bims-enlima Biomed News
on Engineered living materials
Issue of 2026–05–31
58 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool
  1. De Novo Engineered Living Materials via Elastin-Like Polypeptide-Mediated Self-Assembly.
  2. Synthetic DNA circuits for programming cell functions.
  3. Polyketide synthase-based controlled synthesis of polycyclopropanated fuel molecules.
  4. Latent Catalysis as a Platform for Accessing Diverse Material Properties in Vat Photopolymerization 3D Printing.
  5. FABRICATION OF PATTERNED HYDROGELS WITH CONTROLLED MECHANICAL PROPERTIES USING CHEMICALLY MODIFIED RLPS.
  6. Combined biosynthesis and site-specific incorporation of phenylalanine derivatives from aryl aldehydes or carboxylic acids.
  7. Elasticity-gated thermal plasticity via superheating-mediated nucleation and growth in polymer networks.
  8. Biocompatible, Tunable, Multifunctional Adhesive Silk-PDA Composite Films for Modern Labeling Needs.
  9. Entanglement-driven responses through multiscale 3D-printed knits.
  10. Gelatin-based materials with inverse structures: Porous hydrogels compared to hydrogel particles.
  11. Multicolor and Attenuated Light Intensity Responses in Protein Hydrogels Arising from Photoregulated Crosslink Dynamics.
  12. Anaerobic metabolic evolution for homotypic L-valine fermentation.
  13. Plug-and-play assembly of biodegradable ionizable lipids for potent mRNA delivery and gene editing in vivo.
  14. Additive Manufacturing of Ordered Polymer Nanostructures.
  15. Autocatalytic selection of gene functions in synthetic cells.
  16. Dual Jamming of Biobased CNC-Stabilized Bijel Fibers via Continuous Solvent Transfer Induced Phase Separation.
  17. Fabrication of Mechanically Reinforced Photo-Cross-linked Hydrogels with Steep Post-Gelation Threshold Curing via Vinylated Self-Assembling Peptides.
  18. Metal-phenolic networks improve interfacial electron transfer in bio-electrochemical systems.
  19. Closed-Loop Optogenetic Control in a Microplate Reader.
  20. A standardized toolkit for programmable protein secretion and surface display in Bacteroides thetaiotaomicron.
  21. Parallel gene amplification by Cas9 nickase for generating functionally heterogeneous cell populations.
  22. Photoprintable Photothermal Actuators for Spatially Programmable Shape Morphing.
  23. Granular Extracellular Matrix (gECM) Hydrogels Enable Distinct Composition and Mechanics Across Tissue Types for Translation.
  24. Fibrillar Hydrogel Derived from Nanocellulose and a Synthetic Polypeptide.
  25. A Rapidly Self-Healing Composite Hydrogel with Exceptional Impact Resistance Enabled by Synergistic Noncovalent Networks.
  26. Active protein-capturing hydrogel for broad-spectrum pathogen defense.
  27. Dithiolane-Based Reversible "Trojan Tag" For Intracellular Protein Delivery and Prodrug Design.
  28. Mechanochemical and machine-intelligent design of programmable materials: From molecular interactions to macroscale functionality.
  29. Methacrylated gelatin-based conductive self-healing hydrogels: a dual-scale approach for micro- and macro-sized soft materials.
  30. Skin-mimicking biogel-based iontronic sensor with hierarchical bionic coupling for dexterous tactile e-skin.
  31. An engineered closed-shell, two-component, 480-subunit nucleocapsid.
  32. Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells.
  33. Tools For Building Artificial Biological Nanostructures.
  34. Transistors on a roll: 3D circuits built from stacks of flexible membranes.
  35. Engineering high-titer lentiviral vectors for robust expression of RNA-based gene circuits.
  36. Wireless battery-free oxygenation devices enable extended immunosuppression-free islet transplantation in minimally invasive sites.
  37. Emerging Dynamic Polymers for Sustainable Materials.
  38. Closed-Loop Recyclable, Tough, and Solvent-Resistant Electromagnetic Shielding Hydrogel Inspired by Dragonfly.
  39. Enhanced volumetric additive manufacturing via Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerization.
  40. Digital Light Processing of Three-dimensional Liquid Metal Hydrogels.
  41. AI-discovered protein fragments as generalizable regulators of biomolecular condensates.
  42. Self-Strengthening of Force-Adaptive Hydrogels Cross-Linked with Pluronic Micelles through Mechanical Training.
  43. Evolving strategies for lineage tracing: Genetic markers, synthetic barcodes, and natural variants.
  44. Growth in confinement promotes Pseudomonas aeruginosa tolerance to antibiotics.
  45. QuantGUV: Quantifying Encapsulation Efficiency of Small Molecules in Giant Unilamellar Vesicles.
  46. De novo promoters emerge more readily from random DNA than from genomic DNA.
  47. Cell-based cytokine patch for localized immunomodulation and accelerated healing in rodent and porcine wounds.
  48. Move over, AlphaFold: open-source model predicts shape of 1 billion proteins.
  49. Improving multimodal wearable sensing for healthcare with artificial intelligence.
  50. Tuning mitotic recombination with patterned DNA nicks for precision mosaic analysis.
  51. Single step fabrication of muscle bundles for cultivated meat using mechanotransduction: a paradigm shift.
  52. Metabolic feedbacks drive population dynamics and can lead to oscillations among leaf bacteria.
  53. PrEditR: A protein-centric platform for CRISPR-mediated base editor sgRNA design.
  54. A T7 RNAP regulatory toolbox for cell-free network engineering and biosensing applications.
  55. Counting to two: how phages decide between lysis and lysogeny.
  56. Fully Biobased, Robust, and High-Conductivity Hydrogel for High-Fidelity Electrophysiological Monitoring and Deep Learning-Assisted Stroke Rehabilitation.
  57. Lignin-Based Hydrogels for Sustainable Agriculture: Extraction, Design, and Applications.
  58. Zwitterionic Powder-Based Gradient Adhesion-Lubrication Hydrogels for Efficient Hemostasis and Antiadhesion.
  1. ACS Synth Biol. 2026 May 28.
    De Novo Engineered Living Materials via Elastin-Like Polypeptide-Mediated Self-Assembly.
    Sarah B Browning, Davide Prati, Luca Mascia, Paolo Magni, Lorenzo Pasotti, Sara Molinari.
      De novo engineered living materials (ELMs) are cellular systems that self-assemble into macroscopic structures through genetically encoded interactions, offering a route to programmable materials grown directly from living cells. Despite their promise, the molecular design principles that enable scalable self-assembly in de novo ELMs remain poorly understood. Here, we engineer Escherichia coli to display elastin-like polypeptides (ELPs), transforming single cells into self-assembling living materials. By tuning the polarity of ELP sequences, we generate assemblies spanning micrometer- to centimeter-length scales that sediment within a few hours while preserving cellular metabolic activity. We demonstrate the portability of this platform across genetic backgrounds and inducible expression systems and deploy it in an ethanologenic E. coli strain as a proof of principle. In small-scale fermentation settings, ELP-based ELMs enable controllable flocculation, reduce filtration time by more than 3-fold, and maintain ethanol production performance comparable to that of the parental strain. Together, this work establishes ELP surface display as a modular strategy for constructing de novo engineered living materials and defines initial genetic design rules linking molecular-scale interactions to emergent macroscopic organization.
    Keywords:  Escherichia coli; bacterial self-assembly; elastin-like polypeptides; engineered living materials; flocculation; surface display
    DOI:  https://doi.org/10.1021/acssynbio.6c00073
  2. Curr Opin Chem Biol. 2026 May 29. pii: S1367-5931(26)00050-5. [Epub ahead of print]93 102701
    Synthetic DNA circuits for programming cell functions.
    Miao Wang, Wenfeng Tang, Siqi Jiang, Ping Wei.
      Synthetic biology aims to re-engineer living cells into autonomous computational chassis capable of executing sophisticated biological tasks. Within this framework, programmable nucleic acid-based logic networks have emerged as a versatile molecular control layer for constructing intelligent cellular systems, offering unparalleled precision, orthogonality, and interoperability. Here, we highlight recent advances in molecular programming, focusing on the integration of synthetic DNA circuits within cellular environments to achieve logic-gated control of cellular functions. We first delineate the fundamental building blocks-including strand displacement, logic gates, amplifiers and neuromorphic architectures-and then examine strategies for interfacing these components with endogenous pathways. The field is currently witnessing a paradigm shift from ex vivo demonstration to in situ functional implementation, driven by the maturation of nucleic acid-based engineering within synthetic biology. Ultimately, these programmable molecular controllers enable the rational design of cellular behaviors, paving the way for next-generation precision therapeutics and autonomous biomanufacturing.
    DOI:  https://doi.org/10.1016/j.cbpa.2026.102701
  3. Nat Commun. 2026 May 27.
    Polyketide synthase-based controlled synthesis of polycyclopropanated fuel molecules.
    Kevin Yin, Alexander Landera, Namil Lee, Anthony T Iavarone, Suzanne M Kosina, Thomas D Young, Kai Deng, Justin Baerwald, Yan Chen, Jennifer W Gin, Riley Benedict, Yan Chiu, Ezechinyere Ukabiala, Methun Kamruzzaman, Kunal Poorey, Trent R Northen, Christopher J Petzold, Anthe George, Pablo Cruz-Morales, Qingyun Dan, Jay D Keasling.
      Reducing carbon emissions from aviation and long-distance transportation sectors requires the development of sustainable biofuels with suitable energy density, freezing point, and other physical properties. We previously demonstrated biological production of high energy polycyclopropanated fatty acids (POP-FAs, class I) using an iterative polyketide synthase (iPKS) pathway in a Streptomyces host. Here, we used a computational model of fuel properties to identify chain length and cyclopropanation control as critical steps to engineer this iPKS for biofuel applications. We next explored the natural diversity of POP biosynthesis by investigating homologous pathways. Then, by in vivo gene exchange, we determined cyclopropanase (CP) catalysis to be key for POP-FA engineering. Leveraging both natural and engineered pathway product diversity, we demonstrate targeted production of improved POP-FAs, namely shortened POP-FAs with predicted superior freezing point properties for aviation, as well as fully cyclopropane-saturated POP-FAs which should have superior energy-density. These precise and controllable modifications to POP-FA structure open the door for bioproduction of designer POP fuels.
    DOI:  https://doi.org/10.1038/s41467-026-73172-3
  4. Angew Chem Int Ed Engl. 2026 May 26. e5527609
    Latent Catalysis as a Platform for Accessing Diverse Material Properties in Vat Photopolymerization 3D Printing.
    Cali N Colliver, Meredith A Borden, Frank A Leibfarth.
      Vat photopolymerization (VP) 3D printing is an attractive strategy to manufacture customized polymer parts. The properties of printed materials are limited by the need to employ a low viscosity liquid resin and achieve rapid polymerization kinetics. To circumvent this limitation, dual-cure methods have been developed using reagents embedded in the liquid resin formulation; however, the reagent-based approach requires the discovery and optimization of new chemistry for each desired material. Here, we demonstrate a catalytic, dual-cure platform that enables access to both Nylon-6 and polyester interpenetrating networks through VP 3D printing under a universal approach. Structure-reactivity relationships of the latent NHC catalysts led to the identification of a magnesium chloride-NHC adduct as a latent catalyst that is orthogonal to radical polymerization and can be unmasked at elevated temperatures post-printing to initiate ring-opening polymerization of lactones and lactams. This strategy results in access to semicrystalline materials, which are a challenging morphology to access via VP 3D printing, that have attractive mechanical properties and can be printed at high resolution. This work represents the first photochemical-based 3D printing of Nylon-based materials and demonstrates the value of catalytic approaches to access new material properties in VP 3D printing.
    DOI:  https://doi.org/10.1002/anie.5527609
  5. Int Mech Eng Congress Expo. 2026 ;pii: V003T04A040. [Epub ahead of print]3
    FABRICATION OF PATTERNED HYDROGELS WITH CONTROLLED MECHANICAL PROPERTIES USING CHEMICALLY MODIFIED RLPS.
    Ramadan Abouomar, Zameer Hussain Shah, David P Rivas, Sudipta Mallick, Luisa Palmese, Sai S Patkar, Kristi L Kiick, Sambeeta Das.
      In our study, we created hydrogels containing selectively polymerized regions with distinct mechanical properties by photopolymerizing chemically modified resilin-like polypeptides (RLPs) under a variety of conditions. To promote the formation of microstructures, we utilized a poly(ethylene glycol) crosslinker and employed Digital Micromirror Display (DMD) techniques to pattern the hydrogel. The microstructures of the hydrogels were analyzed using various methods, such as confocal microscopy and scanning electron microscopy, while the local mechanical properties were determined through atomic force microscopy (AFM) measurements. Overall, our work demonstrates a versatile approach for creating hydrogels with spatially varying mechanical properties. The mechanical properties, both inside and outside the illuminated region, can furthermore be adjusted by adding a crosslinker. We find that the microstructure of the hydrogel is different when the hydrogel is crosslinked via DMD compared to a UV lamp, providing an additional method for material property control. These results have potential applications in various fields, including tissue engineering and drug delivery, where the ability to precisely control mechanical properties and microstructures is critical for achieving desired outcomes.
    Keywords:  Hydrogels; Light Patterning; Resilin
    DOI:  https://doi.org/10.1115/IMECE2025-164092
  6. Nat Commun. 2026 May 23.
    Combined biosynthesis and site-specific incorporation of phenylalanine derivatives from aryl aldehydes or carboxylic acids.
    Shelby R Anderson, Abigail P Spangler, Amanda M Forti, Michaela A Jones, Roman M Dickey, Aditya M Kunjapur.
      Applications of genetic code expansion (GCE) in live cells are widespread and continually emerging, yet they have been limited by their reliance on the supplementation of non-standard amino acids (nsAAs) to cell culturing media. Here, we report the design of a single engineered bacterial host that performs the steps of phenylalanine derivative semi-synthesis and site-specific incorporation within target proteins. Our platform pathway exhibits broad substrate specificity towards commercially ubiquitous, achiral building blocks of aryl aldehydes or carboxylic acids, producing the family of nsAAs that are most frequently used for GCE. We demonstrate biosynthesis of 12 distinct nsAAs, and we observe combined biosynthesis and incorporation for these chemistries using common orthogonal translation systems (OTSs) based on a fluorescent reporter assay. We additionally show that the combination of nsAA biosynthesis and GCE steps can extend the chemical reach of the intrinsic biological containment strategy of synthetic auxotrophy from reliance on nsAAs to instead reliance on low-cost and achiral building blocks. Our platform should aid industrial-scale manufacturing of proteins that contain nsAAs and democratize access to expensive or commercially unavailable chemistries for labs that lack separations or traditional synthesis expertise.
    DOI:  https://doi.org/10.1038/s41467-026-73618-8
  7. Nat Commun. 2026 May 25.
    Elasticity-gated thermal plasticity via superheating-mediated nucleation and growth in polymer networks.
    Guye Wei, Jiageng Pan, Shunjie Mo, Jian Liao, Liang Gao.
      Living systems encode environmental history into material structure, enabling adaptive response thresholds, a capability lacking in synthetic materials with fixed thermal transitions. We present a thermodynamic approach that programs critical transition temperatures in polymer networks via salt-dependent thermal plasticity. Conditioning poly(vinyl propional) hydrogels at a swelling temperature Ts in Hofmeister-modulated media embeds thermal and saline history into equilibrium water content, which then dictates superheating-mediated nucleation upon heating. Two synergistic mechanisms: temperature-dependent miscibility encodes memory via adaptive swelling, while network elasticity gates nucleation barriers, giving Tc = Ts + ΔT, where ΔT is set by thermal history and salt identity. Structural characterization reveals a hierarchical architecture of tight physical crosslinks and loose co-evolving domains, offering a universal design rule for history-responsive materials. We demonstrate reprogrammable freeze-exposure indicators for vaccine cold-chain monitoring to quantify sub-zero breach severity and duration. This work establishes intelligent matter capable of autonomous sensing, memory, and adaptive actuation.
    DOI:  https://doi.org/10.1038/s41467-026-73606-y
  8. ACS Appl Mater Interfaces. 2026 May 25.
    Biocompatible, Tunable, Multifunctional Adhesive Silk-PDA Composite Films for Modern Labeling Needs.
    Marco Lo Presti, Maxwell W Oulundsen, Noah L Whitney, Chungman Kim, Bryan Hirsch, Nicholas Ostrovsky-Snider, Manini Banerjee, Shonglin Gaekwad, Narendar Gogurla, Fiorenzo G Omenetto.
      Adhesive labels are massively used in production processes and are ubiquitously present in nearly every product. However, their use often complicates the recycling of the materials they are applied to or leads to fragmentation, dispersing microplastics into the environment. We present here biopolymer-based adhesive films suitable for labeling applications by leveraging silk polymorphism in combination with mussel-inspired chemistry. Incorporating dopamine into the polymeric matrix introduces water-triggered adhesive properties and a plasticizing effect. Its utility can be further augmented through the addition of glycerol, which enables the formation of flexible and insoluble adhesive films. The versatility of form and function of the base biomaterial allows reshaping of protein films on demand and to create functional adhesive surfaces with tunable properties, opening possibilities for programmable biomaterial-based interfaces, that can be used either as laminates on a variety of different substrates or as standalone labels. Adhesive strength, preferred breakage interface, and degradation rates in water can all be customized to meet specific requirements underscoring the versatility and applicability of the platform.
    Keywords:  adhesive; biodegradable; dopamine; film; label; packaging; silk fibroin
    DOI:  https://doi.org/10.1021/acsami.6c00850
  9. Proc Natl Acad Sci U S A. 2026 Jun 02. 123(22): e2535708123
    Entanglement-driven responses through multiscale 3D-printed knits.
    Bradley Cline, Catherine Bai, Sehui Jeong, Ling Xu, Yue Wang, James U Surjadi, Carlos M Portela, Tian Chen.
      Filamentous entanglements such as textiles achieve resilience and toughness through topology rather than material composition alone. Yet architected materials rarely exploit dense interlooping and sliding contacts to achieve extraordinary physical behavior. While research across mechanics, architecture, and design has linked stitch structure to physical behavior, a predictive quantitative framework has remained elusive. Here we show that knitting can be reinterpreted as a general strategy for designing three-dimensional entangled solids with programmable mechanics. Using a geometrically exact description of each stitch and multimaterial 3D printing-a topology-agnostic fabrication approach-we create planar and volumetric knits whose loop parameters directly control stiffness, strength, and energy dissipation. The printed fabrics faithfully reproduce the nonlinear, anisotropic, and hysteretic responses of conventional machine-knitted textiles. We identify a simple normalization that collapses stress-strain curves across stitch geometries, yarn architectures, constituent materials, and length scales, unifying the behavior of traditional and 3D-printed knits on a single master curve. Extending the topology into the "Z" or stacking direction yields volumetric knits whose stiffness and dissipation can be tuned by imposed prestrain. Finally, we realize the same architecture from centimeters down to micrometers, culminating in, to our knowledge, the smallest knitted structure ever fabricated. By demonstrating that 3D-printed knits can be interpreted both as a traditional fabric composed of a single yarn and as an architected material with defined periodicity, this work establishes entangled filaments as a foundation for a class of material architectures whose mechanics are encoded in their topology.
    Keywords:  architected materials; filamentous entanglement; knit textiles
    DOI:  https://doi.org/10.1073/pnas.2535708123
  10. Int J Biol Macromol. 2026 May 22. pii: S0141-8130(26)02588-2. [Epub ahead of print] 152661
    Gelatin-based materials with inverse structures: Porous hydrogels compared to hydrogel particles.
    Robin R Benedix, Omar A Abdelaziz, Alexander Southan, Cosima Stubenrauch.
      In this study, we synthesized two different gelatin methacryloyl (GelMA) hydrogels with inverse macroscopic structures and similar hydrogel network structures, i.e. porous hydrogels and hydrogel particles. Inverse macroscopic structures means that the node size of the porous hydrogels equals the diameter of the hydrogel particles. The goal is to design materials with same transport properties but different macroscopic structures. We generated porous hydrogels and hydrogel particles by using microfluidic-based liquid foam and droplet templating. For this purpose, we developed formulations containing a highly modified GelMA (GM10) to obtain hydrogel precursor solutions with low viscosity and high crosslinking ability. Porous hydrogels and hydrogel particles with monodisperse pore and particle sizes, respectively, were obtained. Via X-ray microtomography, we investigated the macroscopic structure and found the size range to generate porous hydrogels and hydrogel particles with inverse macroscopic structures. In addition, similar surface-to-volume ratios for both hydrogels were found. The similarity of the hydrogel network structures of both hydrogels was shown by measuring the equilibrium degree of swelling (EDS) in two different swelling media. Cytotoxicity assays confirmed the cytocompatibility of both hydrogels. These findings establish a foundation for future studies on drug sorption and release of these two hydrogel materials.
    Keywords:  Droplet templating; Foam templating; GelMA; Hydrogel particles; Microfluidics; Porous hydrogels; X-ray microtomography
    DOI:  https://doi.org/10.1016/j.ijbiomac.2026.152661
  11. Angew Chem Int Ed Engl. 2026 May 28. e6692301
    Multicolor and Attenuated Light Intensity Responses in Protein Hydrogels Arising from Photoregulated Crosslink Dynamics.
    Saskia Frank, Seraphine V Wegner.
      Light-responsive hydrogels enable noninvasive, precise, remote control over material properties with great biocompatibility, yet achieving multicolor addressability and dynamic regulation of mechanical properties remains challenging. Most systems rely on single photoswitches and regulate stiffness primarily through changes in crosslinking density. Here, we present a fully protein-based hydrogel that combines multicolor light responsiveness with optical control of crosslink dynamics. The hydrogel includes two visible light-responsive photoceptors: the cyanobacterial phytochrome Cph1, which enables reversible red/far-red light-controlled crosslinking, and CarH, which introduces irreversible green light-induced gel-sol transitions. Remarkably, Cph1-based hydrogels exhibited an attenuated red light intensity response, forming stiffer networks under low-intensity illumination than under high-intensity light and show a subsequent dark-adaptation with stiffening once red light illumination is stopped. This counterintuitive behavior arises from light-driven bidirectional photoisomerization that modulates crosslink lifetimes without altering the photostationary state composition. Together, these findings establish orthogonally addressable reversible and irreversible crosslinks and photoregulated crosslink dynamics as new design principles for multicolor light-responsive biomaterials.
    Keywords:  Cph1; attenuated response; multicolor; photoresponsive; protein hydrogel
    DOI:  https://doi.org/10.1002/anie.6692301
  12. Nat Commun. 2026 May 29.
    Anaerobic metabolic evolution for homotypic L-valine fermentation.
    Siqi Yang, Fenghui Qian, Tao Wu, Bingbing Sun, Huiqi He, Meng Qiao, Feng Dong, Peng Gao, Zhao Chen, Ying Zhang, Junjie Yang, Yu Jiang, Sheng Yang.
      L-valine is an essential amino acid for animal nutrition. Ideally, it can be produced from D-glucose through homotypic L-valine fermentation in a growth-coupled manner. To date, no known microorganism, native or engineered, can grow on D-glucose and ammonia anaerobically with L-valine as the sole product. Here, we direct the metabolic flux through a reinforced L-valine synthetic pathway by blocking mixed-acid fermentation and L-alanine synthesis reactions to create an NADH driving force in Escherichia coli. We further evolve the engineered strain to debottleneck growth constraints by anaerobic growth rescue. The resulting evolved hyper-valine producer converts D-glucose in a 320 m3 reactor to 83.6 g/L L-valine within 60 h, reaching a yield of 0.55 g/g glucose (85% of the theoretical maximum). Through reverse engineering, we identify that more than a 10-fold improvement in anaerobic growth and L-valine production rate arises from the amplified L-valine synthetic pathway, the additional electron sinks and reprogramming of global regulation. Together, we changed the way of L-valine production into homotypic L-valine fermentation and demonstrate how E. coli variants adapted their metabolic activities and transcriptional regulation to boost fitness in an anoxic condition, with L-valine synthesis serving as the primary NADH-consuming pathway.
    DOI:  https://doi.org/10.1038/s41467-026-73619-7
  13. Proc Natl Acad Sci U S A. 2026 Jun 02. 123(22): e2528144123
    Plug-and-play assembly of biodegradable ionizable lipids for potent mRNA delivery and gene editing in vivo.
    Xuexiang Han, Ying Xu, Adele S Ricciardi, Junchao Xu, Yan Xiang, Rohan Palanki, Vivek Chowdhary, Lulu Xue, Ningqiang Gong, Mohamad-Gabriel Alameh, William H Peranteau, James M Wilson, Daniel Reker, Drew Weissman, Michael J Mitchell.
      mRNA-based gene editing therapeutics offer the potential to permanently cure diseases but are hindered by suboptimal delivery platforms. Here, we devise a robust combinatorial chemistry for the plug-and-play assembly of structurally diverse biodegradable ionizable lipids from amines/thiols and dialkyl maleates. After screening 500 ionizable lipids, we obtained structure-activity relationships essential for effective in vitro mRNA delivery with the help of machine learning. Furthermore, we identified a lead ionizable lipid candidate that produced potent lipid nanoparticles for the delivery of various gene editing tools in wild-type and genetically modified mice compared to literature and industry benchmark lipid nanoparticles. Mechanistically, our lipid nanoparticles show favorable physicochemical properties, which could synergistically contribute to the superior delivery performance. This study highlights the utility of this synthetic method as well as the generality of this platform for potent in vivo gene editing.
    Keywords:  CRISPR; gene editing; ionizable lipid; lipid nanoparticle; mRNA delivery
    DOI:  https://doi.org/10.1073/pnas.2528144123
  14. Adv Mater. 2026 May 23. e73395
    Additive Manufacturing of Ordered Polymer Nanostructures.
    Di Wu, Kun Zhou, Kenny Lee, Yuan Xiu, Carol Hiu Wai Yan, Khoon S Lim, Cyrille Boyer.
      Additive manufacturing (3D printing) allows the fabrication of complex 3D geometries, yet the integration of long-range ordered nanostructures within printed materials remains a fundamental challenge. In vat photopolymerization, rapid crosslinking kinetics typically arrest block copolymers in kinetically trapped, disordered morphologies. Here, we introduce Polymerization-Induced Arrangement of Nanostructures with Order-tunability (PIANO), a strategy that overcomes this kinetic mismatch by decoupling nanoscale ordering from network formation. PIANO utilizes a mobility mediator, ethylene glycol, to enhance polymer chain mobility, enabling rapid in situ ordering, while maintaining a hydrogen-bonding network capable of sustaining 3D printing stresses. This approach yields tunable lamellar and hexagonally packed cylindrical morphologies with domain spacings of 20-60 nm. Furthermore, ethylene glycol acts as a latent crosslinker during post-printing annealing, locking the ordered nanostructure while enhancing macroscopic mechanical strength. By reconciling the divergent timescales of molecular self-assembly and additive manufacturing, this strategy provides a robust platform for the hierarchical design of functional systems.
    Keywords:  3D printing; block copolymers; nanostructures; photopolymerization; self‐assembly
    DOI:  https://doi.org/10.1002/adma.73395
  15. Commun Biol. 2026 May 27.
    Autocatalytic selection of gene functions in synthetic cells.
    Laura Sierra Heras, Christophe Danelon.
      The integration of biological functions into a single operating system is considered a major challenge in the construction of a synthetic cell. We present autocatalytic selection (ACS) of gene functions as a driver for integrating biological modules in vitro. A gene of interest (GOI) is introduced into a minimal DNA self-replicator and the function of the GOI is linked to transcription, translation or DNA replication through a positive feedback loop. As the encoded function eventually promotes DNA self-replication, the gene variants with greater activity are selected. Using different coupling mechanisms, we demonstrate ACS of three functions: transcription, in situ regeneration of dGTP from dGMP to support DNA replication, and β-galactosidase activity. The latter example illustrates how a function that is not directly related to the Central Dogma can be selected. In addition, we show that metabolically active replicators can be enriched from a library of variants generated by random mutagenesis. This work paves the way for ACS-driven Darwinian evolution of virtually any biomolecule in vitro, streamlining the construction of increasingly complex synthetic cells as well as the engineering of biotechnologically relevant enzymes.
    DOI:  https://doi.org/10.1038/s42003-026-10372-z
  16. ACS Appl Mater Interfaces. 2026 May 25.
    Dual Jamming of Biobased CNC-Stabilized Bijel Fibers via Continuous Solvent Transfer Induced Phase Separation.
    Minke Yang, Guang Gao, Xin Shu, Yi Lu, Orlando J Rojas.
      Bicontinuous nanoparticle-stabilized emulsions are formed by mixing two immiscible liquids with a cosolvent, followed by inducing phase separation within the spinodal regime and kinetically arresting the evolving morphology with colloidal nanoparticles. Here, we demonstrate that biobased, rod-like cellulose nanocrystals (CNCs) can stabilize bicontinuous emulsion gels at a low particle loading of 3 wt % through combined inter- and intraphase jamming, yielding characteristic domain sizes of approximately 10 μm. The use of 1-propanol as a cosolvent promotes CNC dispersion prior to and during solvent transfer, enabling the continuous production of CNC-stabilized bicontinuous emulsion gels as the segmented fibers (1-2 cm) and continuous filaments exceeding 25 cm in length. A key finding is that surfactant-specific access to near-neutral wetting is identified as a practical control lever for CNC, and DDAB enables the robust filament formation. The resulting porous, biphasic CNC network supports efficient crossflow mass transfer, providing a promising platform for interfacial transport and reaction processes. This work established a scalable route to sustainable material design from anisotropic nanoparticles.
    Keywords:  Pickering bicontinuous emulsions; cellulose nanocrystals (CNCs); interfacial jamming; microreaction media; solvent-transfer induced phase separation (STRIPS)
    DOI:  https://doi.org/10.1021/acsami.6c04985
  17. Adv Mater. 2026 May 28. e73506
    Fabrication of Mechanically Reinforced Photo-Cross-linked Hydrogels with Steep Post-Gelation Threshold Curing via Vinylated Self-Assembling Peptides.
    Yunlong Yang, Shujian Li, Bingkun Bao, Ting Chen, Qingmei Zeng, Yu Zhu, Baima Danzeng, Xueli Hu, Qiuning Lin, Linyong Zhu, Yun Liao.
      Tomographic volumetric 3D printing (TVP) enables the ultrafast, layer-free fabrication of hydrogel devices. However, its widespread application is hindered by insufficient curing within the narrow light-dose processing window, which ultimately compromises the fidelity and stability of the printed hydrogels. To address this challenge, we introduce a peptide self-assembly-mediated polymerization strategy to engineer mechanically reinforced hydrogels that exhibit steep curing immediately following the gelation threshold. In our approach, vinylated self-assembling peptides (vSAPs) are conjugated to tetra-arm polyethylene glycol macromers (vSAP-macromers). The self-assembly of vSAP-macromers induces nanoscale spatial confinement of vinyl groups, which substantially shortens the diffusion distance for radical propagation. Consequently, vSAP-macromers exhibit steep conversion and rapid network formation once the light dose exceeds the polymerization threshold. Moreover, the incorporation of vSAPs induces a potential nanoreinforced network, leading to substantial mechanical reinforcement. Owing to these features, vSAP-macromers ensure the in-process stability of hydrogel constructs under restricted light doses. Consequently, this leads to improvements in both the printing fidelity and mechanical performance of the final TVP-fabricated hydrogels. Collectively, this work offers a generalizable design framework for tailoring high-performance hydrogels for TVP and a solution to resolve the polymerization kinetic mismatch in hydrogel volumetric printing.
    Keywords:  Free radical‐based polymerization; Nanoreinforcement; Peptide self‐assembly; Photo‐crosslinking hydrogel; Tomographic volumetric 3D printing
    DOI:  https://doi.org/10.1002/adma.73506
  18. NPJ Biosens. 2026 ;3(1): 32
    Metal-phenolic networks improve interfacial electron transfer in bio-electrochemical systems.
    Sunanda Dey, Madeleine E Laws, Songyi Yeon, Jesus M Lopez Baltazar, Chao-Chi Kuo, Ariel L Furst.
      Multi-enzyme electrocatalytic cascades often suffer from poor electron-transfer efficiency, limiting their utility. We overcome this critical challenge by integrating an interfacial metal-phenolic network (MPN) layer with tunable properties based on the metal and polyphenol employed. Upon electropolymerization, MPNs provide a stable matrix for co-immobilizing glucose oxidase and horseradish peroxidase, enhancing their tandem activity. Through systematic evaluation of the impact of MPN composition on electron transfer, we demonstrate the tunability of these materials for cascade-specific optimization. This simple material is expected to support diverse enzymatic reactions important for technologies ranging from bioenergy to biosensing.
    Keywords:  Chemistry; Energy science and technology; Materials science
    DOI:  https://doi.org/10.1038/s44328-026-00100-2
  19. ACS Synth Biol. 2026 May 25.
    Closed-Loop Optogenetic Control in a Microplate Reader.
    Hari R Namboothiri, Krishna Pochana, Bhavya Jaiswal, Azita Emami, Chelsea Y Hu.
      Optogenetics integrates living cells and electronics into powerful cell-silicon systems, but prototyping their dynamics remains challenging. Current tools either require robotic liquid transfers into flow cytometers or rely on custom sensors with a narrow dynamic range that limits controller performance. Additionally, current successful optogenetic feedback controllers only operate in chemostats or microfluidic devices that enforce constant growth, because models for growth-aware controller design in batch culture are lacking. Here, we present LEMOS, a low-cost LED-embedded microplate that runs inside a commercial microplate reader. Coupled with a growth-aware multiscale model of gene expression for controller tuning, this platform enables rapid design-build-test-learn cycles for cell-silicon systems. We demonstrate closed-loop set point tracking of gene expression in batch cultures within a standard microplate reader and show how growth dynamics complicate controller selection and tuning. Together, this platform reduces setup overhead and speeds up iteration, enabling accurate real-time optogenetic feedback control.
    Keywords:  LEMOS; cybergenetics; growth-aware gene expression dynamics; optogenetic feedback control
    DOI:  https://doi.org/10.1021/acssynbio.6c00003
  20. bioRxiv. 2026 May 14. pii: 2026.05.12.724727. [Epub ahead of print]
    A standardized toolkit for programmable protein secretion and surface display in Bacteroides thetaiotaomicron.
    Yu-Hsuan Yeh, Shannon J Sirk.
      Bacteroides thetaiotaomicron ( Bt ), a dominant bacterial species in the human gut, is a promising chassis for engineering in situ therapeutic delivery systems. Previously, we developed a secretion toolkit composed of endogenous lipoprotein signal peptides (SPs) and full-length secretory proteins from Bt . However, due to variations in length, structure, and amino-acid sequence, these SPs exhibited inconsistent secretion efficiencies across different cargo proteins. Because the activity of individual SP-cargo pairs is not readily predictable, screening and optimization is often required to achieve target secretion titers. To enhance the utility of our toolbox, we studied the impact of different SP sequence components on protein secretion, then applied this knowledge to develop a standardized toolkit to and enable predictable and tunable protein secretion across diverse SP-cargo pairs. To achieve this, we first identified the lipoprotein export sequence (LES) as the key determinant of efficient secretion of heterologous proteins by lipoprotein SPs. We next performed mutagenesis on the LES region of a representative lipoprotein SP to generate a pool of mutants featuring a standardized SP backbone with diversified LES regions. Screening and characterization of this mutant pool revealed a charge-dependent regulation of both secretion and surface display of heterologous cargo proteins. From these findings, we established a toolkit with improved tunability, enhanced predictability, and surface display capabilities that minimizes the need for iterative screening when developing protein secreting gene circuits for Bt and other Bacteroides species. By enhancing both the flexibility and control of therapeutic protein output, these results expand the potential of engineered living therapeutic applications, particularly those requiring tunable dosing or surface presentation of proteins.
    DOI:  https://doi.org/10.64898/2026.05.12.724727
  21. Cell Rep Methods. 2026 May 25. pii: S2667-2375(26)00167-0. [Epub ahead of print] 101467
    Parallel gene amplification by Cas9 nickase for generating functionally heterogeneous cell populations.
    Hiroaki Takesue, Satoshi Okada, Takashi Ito.
      Genetic diversity underlies adaptive evolution. Because genes often act in concert to execute biological processes, the dosage stoichiometry among cooperating genes represents an additional layer of diversity beyond sequence variation. We therefore hypothesized that combinatorial randomization of gene copy numbers could generate cell populations enriched for functional heterogeneity and evolutionary potential. To test this idea, we extended our previously developed Cas9 nickase-based gene amplification method, break-induced replication-mediated tandem repeat expansion (BITREx), to simultaneously target multiple genes. Applying parallel BITREx to three carotenogenic genes introduced into the budding yeast Saccharomyces cerevisiae, we generated a cell population exhibiting broad variation in both absolute copy numbers and their stoichiometric ratios. This population enabled the identification of elite genotypes-specific copy number combinations that conferred enhanced β-carotene production. These results suggest that parallel BITREx is a versatile strategy for increasing functional heterogeneity in cell populations, with potential applications in both basic and applied research.
    Keywords:  BITREx; CP: biotechnology; CP: systems biology; break-induced replication; genome editing; pathway; yeast
    DOI:  https://doi.org/10.1016/j.crmeth.2026.101467
  22. ACS Nano. 2026 May 28.
    Photoprintable Photothermal Actuators for Spatially Programmable Shape Morphing.
    Zepeng Cai, Feng Jiang, Zuyang Ye, Licheng Cao, Jinxing Chen, Yadong Yin.
      Photothermal actuation holds great potential for developing smart materials capable of complex shape transformations. Conventional approaches to achieve these transformations often depend on selective light illumination or spatial engineering of mechanical modulus to induce localized responses, which lead to high design complexity and limited programmability. Using photocatalytic nanoparticles, we introduce a photoprintable strategy for fabricating photoactuators with spatially controlled plasmonic nanoparticle distributions and pattern line widths as small as 20 μm. This design enables localized photothermal heating and, therefore, complex, programmable shape morphing. To prove the concept, we demonstrate the construction of a bimorph actuator that can transform from a flat, two-dimensional shape to a three-dimensional helical form, capable of controlled object transport by mimicking the gripping behavior of tendril-climbing plants. Additionally, microscale photoprinting enables localized photothermal actuation that drives three-dimensional morphing and supports the miniaturization of soft actuators under uniform illumination. This photoprinting approach offers a straightforward yet effective platform for designing smart materials and devices with programmable and biomimetic shape transformations.
    Keywords:  bimorph; photoprinting; photothermal actuators; plasmonic nanoparticles; smart materials
    DOI:  https://doi.org/10.1021/acsnano.6c06213
  23. bioRxiv. 2026 May 11. pii: 2026.05.06.723348. [Epub ahead of print]
    Granular Extracellular Matrix (gECM) Hydrogels Enable Distinct Composition and Mechanics Across Tissue Types for Translation.
    Juliet O Heye, Shannon A Blanco, Stephanie E Schneider, Aseem M Visal, Faith O Olulana, Emily Y Miller, Jeanne E Barthold, Carson J Bruns, Maxwell C McCabe, Sean P Maroney, Kirk C Hansen, Corey P Neu.
      Biomaterials-based tissue engineering aims to recapitulate native tissue architecture and function for both clinical repair and advanced in vitro models. While improvements in biomaterials have been made, including granular hydrogels and ECM-derived scaffolds, current biomaterials lack intentional design choices for effective translation, including regulatory considerations, practical extrusion delivery, and biomimetic characteristics. Here, we develop and characterize a library of granular ECM (gECM) biomaterials for five key tissues (cartilage, bone, skin, liver, and kidney), in which ECM particles are densely packed within a hyaluronic acid hydrogel. We optimize tissue processing methods that preserve proteomic content and structure while also aligning with scale-up manufacturing and regulatory guidelines. We show that gECM hydrogels can be molded, extruded, and 3D-printed while retaining their shape, and they stabilize at physiological temperature and pH. Lastly, we demonstrate that bulk gECM mechanics are driven by tissue type, and gECM hydrogels support viability, proliferation, and tissue-specific cellular activity. Together, these findings establish gECM hydrogels as a translational and biomimetic platform for clinical tissue repair and complex in vitro models.
    DOI:  https://doi.org/10.64898/2026.05.06.723348
  24. Langmuir. 2026 May 26.
    Fibrillar Hydrogel Derived from Nanocellulose and a Synthetic Polypeptide.
    Baichuan Kou, Jue Gong, Bexi M Bustillo-Perez, Elizaveta A Gusarova, Zheyuan Miao, Tianyi Wu, Tianjia Yang, Dianoosh Kalhori, Mitchell A Winnik, Eugenia Kumacheva.
      Hydrogels derived from synthetic polypeptides hold promise as biomaterials for tissue engineering and cell culture; however, they lack a fibrillar structure characteristic for the native extracellular matrix. Here, we report a fibrillar hydrogel formed by aldehyde-modified cellulose nanocrystals and poly(γ-propargyl-l-glutamate) that was prepared by ring-opening polymerization of the N-carboxyanhydride monomer and functionalized with diethylene glycol groups and amino groups. In the hydrogel, the polymer retained the α-helical secondary structure of the polypeptide backbone. The mechanical properties of the hydrogel were varied by changing the aldehyde to amino group molar concentration ratio. Human dermal fibroblasts cultured on this hydrogel showed good adherence and metabolic activity. This work should stimulate further studies on the synthesis and applications of synthetic polypeptide-derived biomimetic fibrillar hydrogels.
    DOI:  https://doi.org/10.1021/acs.langmuir.6c01201
  25. ACS Appl Mater Interfaces. 2026 May 28.
    A Rapidly Self-Healing Composite Hydrogel with Exceptional Impact Resistance Enabled by Synergistic Noncovalent Networks.
    Caihui Cui, Lan Yao, Songtao Liu, Heng Yi, Zihui Meng, Min Xue.
      Impact-resistant materials are vital for protection but often lack the combination of flexibility, strength, and reusability. Herein, we developed a self-healing hydrogel composite engineered through a hierarchical noncovalent strategy. By hydrophobic associations, electrostatic interactions, and hydrogen bonds in synergy, the material circumvents the traditional trade-off between mechanical strength and self-healing. The resulting composite exhibits exceptional mechanical performance, including ultrahigh tensile strength of 40 MPa, exceptional toughness of 177 MJ m-3, and outstanding puncture resistance of 478 N. Meanwhile, the inclusion of PDAP provided the hydrogel with rapid, on-demand self-healing properties via the photothermal effect under NIR irradiation, achieving an efficiency exceeding 99% within 15 min. Furthermore, this hydrogel exhibits strain-dependent ionic conductivity and NIR-induced conductivity recovery. By merging the sensing and reparable capabilities of hydrogels with their robust impact and puncture resistance, this innovative material paves the way for advanced protective applications, such as high-performance sportswear and next-generation ballistic armor.
    Keywords:  hydrogels; impact resistance; near-infrared triggered; noncovalent interaction; self-healing
    DOI:  https://doi.org/10.1021/acsami.6c05429
  26. Sci Adv. 2026 May 29. 12(22): eaed2483
    Active protein-capturing hydrogel for broad-spectrum pathogen defense.
    Jiaming Liu, Shiqi Hu, Mengrui Liu, Savannah Weihang Zhang, Na Yan, Xuan Mei, Dashuai Zhu, Ming Shen, Ke Cheng.
      Proteinaceous agents, including viral particles and allergenic proteins, play central roles in infection, inflammation, and immune dysregulation, yet few materials can broadly neutralize them through direct protein capture. Here, we present an inhalable protein trap (IPT), an active hydrogel that rapidly immobilizes diverse amine-containing biomolecules via NHS-amine chemistry. Structural optimization enables IPT to stably incorporate a high density of reactive NHS esters that remain functional under physiological conditions, allowing efficient protein capture at mucosal surfaces. Upon hydration, powdery IPT rapidly forms an active barrier that covalently traps proteins and proteinaceous particles within minutes. This nonselective capture mechanism allows IPT to bind viral particles, allergens released from pollen or fungi, and soluble immune mediators such as histamine. Across multiple animal models, including allergic rhinitis, pollen-induced allergy, and viral infection, IPT consistently outperformed commercial barrier sprays in blocking pathogenic proteins and mitigating disease progression. These results establish IPT as a versatile platform for broad-spectrum protection at biological interfaces.
    DOI:  https://doi.org/10.1126/sciadv.aed2483
  27. ACS Appl Mater Interfaces. 2026 May 29.
    Dithiolane-Based Reversible "Trojan Tag" For Intracellular Protein Delivery and Prodrug Design.
    Yahui He, Xiaoman Yu, Yuanhao Dai, Haoran Cai, Jianhua Lu, Hua Lu.
      Prodrug strategies for protein therapeutics can enable spatiotemporal control, minimize off-target effects and improve safety. However, a universal chemical platform that concurrently enables reversible activity switching and efficient delivery remains a challenge. Here, we introduce a dithiolane-based "Trojan tag" (DTL tag) as a simple, multifunctional tool for constructing modular protein prodrugs with traceless intracellular activation. The DTL tag promotes efficient cellular internalization of diverse proteins, independent of size and isoelectric point. When applied to the anti-PD-L1 (programmed cell death ligand 1) nanobody, the DTL tag enhanced internalization of the resulting complex, effectively trimming PD-L1 from tumor cell surfaces. Furthermore, the tag served as a reduction-triggered activity switch for enzymes like luciferase and RNase A, enabling their efficient delivery and subsequent functional reactivation. Notably, the DTL tag synergized with commercial transfection reagents to enhance cytosolic delivery of RNase A, leading to enhanced cancer cell killing. This straightforward DTL platform streamlines the creation of smart protein prodrugs, offering a new strategy for developing protein prodrugs.
    Keywords:  dithiolane; intracellular delivery; prodrug; protein therapeutics; traceless release
    DOI:  https://doi.org/10.1021/acsami.6c02118
  28. Mater Today Bio. 2026 Jun;38 103188
    Mechanochemical and machine-intelligent design of programmable materials: From molecular interactions to macroscale functionality.
    Mitra Najafloo, Leila Naji, Christoph Eberl.
      Programmable materials are an emerging class of matter capable of dynamically altering their properties, structure, or function in response to external stimuli. While most research has treated chemical and mechanical responsiveness separately, integrating these domains through mechanochemical design opens new avenues for intelligent, adaptive systems. This review explores how chemical reactivity and molecular interactions can be harnessed alongside mechanical deformation to create materials with controllable behavior across multiple scales. Key topics include force-activated molecular units (mechanophores), stress-guided chemical patterning, and materials whose structure-function relationships evolve under load. We highlight the role of machine intelligence in accelerating the discovery and optimization of programmable metamaterials, emphasizing inverse design, data-driven property prediction, and autonomous adaptation. Applications in soft robotics, shape-memory systems, self-healing materials, and smart coatings are discussed, focusing on chemomechanical feedback loops enhanced by computational tools. Multiscale modeling approaches that integrate chemical kinetics, mechanical stress analysis, and AI-guided generative design are also reviewed. By bridging polymer science, molecular chemistry, mechanical engineering, and artificial intelligence, this framework enables the design of materials that are not only responsive but predictive and self-evolving. Current challenges including scalability, reversibility, and durability are considered, alongside future directions toward biologically inspired, resilient material systems.
    Keywords:  Machine intelligence; Mechanochemistry; Programmable materials; Smart materials; Stimuli-responsive polymers
    DOI:  https://doi.org/10.1016/j.mtbio.2026.103188
  29. RSC Appl Polym. 2026 Mar 20.
    Methacrylated gelatin-based conductive self-healing hydrogels: a dual-scale approach for micro- and macro-sized soft materials.
    Didem Aycan, Maria Regato-Herbella, Fereydoon Taheri, Angeles De la Cruz-García, Sebastian Weber, Neslihan Alemdar, Christine Selhuber-Unkel.
      Soft robotic microsystems, inspired by the flexibility of biological structures, have gained significant research interest due to their ability to navigate complex environments with high adaptability. Electroconductive hydrogels (ECHs) have emerged as promising materials for these systems, offering intrinsic softness, biocompatibility, and electrical conductivity. Here, we present an electroconductive hydrogel with multifunctionality developed using a dual-component conductive strategy, incorporating polyaniline (PANI)-silver (Ag) nanoparticles into a methacrylated gelatin (GelMa) network. The hydrogel was fabricated at two different length scales using complementary fabrication techniques. UV crosslinking was employed to produce macroscale hydrogels, while two-photon lithography was used to demonstrate the feasibility of fabricating microscale structures from the same material system. In addition to their structural versatility, the hydrogels exhibited self-healing behavior that enables autonomous recovery of both mechanical and electrical functionalities after damage, which is important for long-term operation in dynamic environments. Comprehensive characterization, including morphological, electrical, mechanical, and biological tests, confirmed the conductivity, cytocompatibility, and tunable mechanical properties of the hydrogel. The results suggest that this biopolymer-based, electroconductive hydrogel with self-healing ability is a highly promising candidate for next-generation soft robotic systems, offering a durable, adaptable, and bio-integrated solution for further soft robotic applications at both macro- and micro-scales.
    DOI:  https://doi.org/10.1039/d5lp00406c
  30. Nat Commun. 2026 May 26.
    Skin-mimicking biogel-based iontronic sensor with hierarchical bionic coupling for dexterous tactile e-skin.
    Yidan Chen, Shu Wang, Xilu Ye, Chenghui Lv, Jialin Wei, Yingxin Zhang, Jianfeng Ping, Yibin Ying, Lingyi Lan.
      The human fingertip skin, with its interlocked epidermal-dermal architecture and dense tactile receptors, enables unique perception and inspires the design of innovative electronic skin (e-skin). However, most e-skin materials fail to replicate the hierarchical integration of composition, structure, and function found in natural skin. Drawing direct inspiration from the dermal extracellular matrix-a composite hydrogel reinforced by a collagen-hyaluronic acid, here we report an e-skin that mimics key composition and architectural features of human skin. By incorporating sodium lactate and montmorillonite nanosheets into a gelatin matrix, we engineer a biomimic gel with mechanical and hydration properties similar to those of natural skin through dynamic ionic crosslinking and hydrogen bond networks. The microstructure resembling the dermal papillae is designed using a sandpaper-templating strategy. The resulting iontronic sensor achieves high sensitivity (466.3 kPa-1), rapid response (47 ms), and a wide pressure detection range (20 Pa-2000 kPa). We further develop a stretchable, ultrathin, hand-shaped iontronic sensor array that integrates seamlessly with a dexterous robotic hand, achieving precise, nondestructive grasping and high-fidelity, multichannel pressure mapping.
    DOI:  https://doi.org/10.1038/s41467-026-73736-3
  31. Proc Natl Acad Sci U S A. 2026 Jun 02. 123(22): e2530090123
    An engineered closed-shell, two-component, 480-subunit nucleocapsid.
    Mikail D Levasseur, Naohiro Terasaka, Angela Steinauer, Stephan Tetter, Sara Pfister, Beat H Meier, Donald Hilvert.
      Self-assembling protein cages are valuable nanoscale containers for biotechnology and medical applications. Two-component systems are especially attractive due to their potential for functional complexity. In this study, we demonstrate that the subunits of the 240-subunit nucleocapsid NC-4, which was previously evolved to package and protect its encoding mRNA, can be split into two fragments without disrupting cage assembly or structure, generating a two-component, 480-subunit capsid. This modification introduces additional termini on the cage's exterior surface, creating opportunities for functionalization. We exploited these new sites by genetically appending peptide and protein tags to the exterior surface of split NC-4 (spNC-4), enabling site-specific glycosylation via posttranslational modification and cell-specific delivery by targeted antibody recruitment. Our findings broaden the utility of the NC-4 nucleocapsid. By extension, splitting related protein compartments that bind diverse cargoes could offer a robust platform for biotechnological applications requiring simultaneous encapsulation and customizable surface modification.
    Keywords:  cryo-EM; nucleocapsid; protein cage; protein engineering; solid-state NMR
    DOI:  https://doi.org/10.1073/pnas.2530090123
  32. Proc Natl Acad Sci U S A. 2026 Jun 02. 123(22): e2536003123
    Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells.
    Andrew L Sabol, Amanuella A Mengiste, Prashant Singh, Vedagopuram Sreekanth, Samuel J Hendel, Minh Thuan Nguyen Tran, Anton M Barybin, Santosh Chaudhary, Ra'Mal M Harris, Kristi E Liivak, Zachary C Severance, Cale M Locicero, Karishma Kailass, Chaiheon Lee, Lucy Qinghua Xu, Vincent L Butty, Amit Choudhary, Matthew D Shoulders.
      Engineering CRISPR-Cas systems for improved or altered function is critical to both research and therapeutic applications. Unfortunately, most optimization, especially directed evolution in bacterial hosts, fails to capture the functional requirements of the complex mammalian cellular milieu, where activity is usually required. Robust strategies to enable continuous directed evolution of genome-targeting agents directly in human cells remain lacking. Here, we introduce CRISPR-MACE (Mammalian cell-enabled Adenovirus-assisted Continuous Evolution) as a foundational technology to address this need. CRISPR-MACE integrates virus-based continuous evolution with anti-CRISPR-based tunable selection to generate Streptococcus pyogenes Cas9 variants with both increased and decreased DNA binding capacity and nearly 1,000-fold-enhanced resistance to AcrIIA4, the strongest known inhibitor of SpCas9. Notably, across independent evolution campaigns, the same Cas9 gatekeeper mutation reproducibly emerged first, enabling subsequent adaptive steps along two interdependent axes of Cas9 function. In addition to advancing CRISPR technologies, this work establishes key principles and synthetic circuits for continuously evolving CRISPR-Cas systems directly in human cells.
    Keywords:  CRISPR-Cas9; anti-CRISPR; directed evolution; protein engineering; synthetic biology
    DOI:  https://doi.org/10.1073/pnas.2536003123
  33. ACS Nano. 2026 May 28.
    Tools For Building Artificial Biological Nanostructures.
    Thomas S Bradford, Sarah Hutchings, Jonathon D Liston, Zuzanna Pakosz-Stepien, Artemis Sanderson, Ahmed Shaukat, Adam Bentham, Ting-Yu Lin, Piotr Stepien, Jonathan G Heddle.
      Biological nanostructures and nanomachines encompass a wide range of natural assemblies from the smallest prokaryotes to viruses, enzymes, and subcellular compartments. Their capabilities are impressive, including replication, locomotion, and catalysis. To be able to design and produce modified or wholly artificial versions of such systems using biological molecules (proteins, nucleic acids, and lipids) is a long-term goal of engineering biology. However, their complexity makes the design and prediction of their properties challenging, while production, purification, and testing can also be difficult. In recent years, new approaches have been developed to facilitate these processes. Here, we review tools for designing biological molecules, highlighting their capabilities and giving examples of their successful application. Finally, we present possible capabilities of future tools and challenges to their development.
    Keywords:  DNA nanotechnology; DNA origami; RNA origami; biological nanomachines; engineering biology; machine learning; programmable molecules; protein design
    DOI:  https://doi.org/10.1021/acsnano.5c14315
  34. Nature. 2026 May 27.
    Transistors on a roll: 3D circuits built from stacks of flexible membranes.
    Veeresh Deshpande.
      
    Keywords:  Electrical and electronic engineering; Materials science; Technology
    DOI:  https://doi.org/10.1038/d41586-026-01413-y
  35. bioRxiv. 2026 May 13. pii: 2026.05.12.724401. [Epub ahead of print]
    Engineering high-titer lentiviral vectors for robust expression of RNA-based gene circuits.
    Kasey S Love, Brittany A Lende-Dorn, Kate E Galloway.
      Lentiviral vectors enable efficient delivery of genetic cargoes for gene and cell therapies. With their ∼10-kb packaging limit, lentiviral vectors can encode multiple transcription units, supporting delivery of compact gene circuits. RNA-based devices offer highly compact control including ligand-responsive induction and closed-loop regulation. However, RNA devices such as ribozymes and splicing switches may interfere with vector production via activity on the single-stranded RNA genome. Here, we examine the impact of gene syntax and genetic parts to define design strategies for two-gene vectors encoding RNA devices. We find that titer decreases with genetic parts that interfere with transcription or processing of the viral transcript during production. Compared to initial vectors, our best-performing design boosts titer more than 30-fold, enabling fine-scale tuning of expression to optimize cell-fate conversion within a nonmonotonic landscape. Together, this work illuminates principles for constructing two-gene lentiviral vectors with both high titer and robust expression, enhancing efficacy for downstream applications.
    DOI:  https://doi.org/10.64898/2026.05.12.724401
  36. Device. 2026 May 15. pii: 101084. [Epub ahead of print]4(5):
    Wireless battery-free oxygenation devices enable extended immunosuppression-free islet transplantation in minimally invasive sites.
    Siddharth R Krishnan, Matthew A Bochenek, Jingwen Pan, Shravika Pendyala, Shek Nga Chan, Claudia Liu, Emily Prokop, Nathaniel Hogrebe, Peter D Rios, Daisy Lopez, Shaunak Potdar, Derin Gumustop, Brian S Her, Laura O'Keeffe, Jeffrey R Millman, Jose Oberholzer, Robert Langer, Daniel G Anderson.
      Here, we develop a next-generation wireless, battery-free oxygen generating O2-Macrodevice and wearable power transfer platform that can enable long-term immune protection and subcutaneous function of therapeutic cells. We demonstrate this device supports xenogeneic islet transplantation in C57BL/6J mice evidenced by 90-day diabetes reversal and glucose responsiveness in vivo. We also show partial glycemic control via high-density (>8,000 islets/cm2) human stem-cell derived islets (SC-islets) without immune-suppression in subcutaneous sites for 90 days. Additionally, we confirmed the device supports allogenic islet cell survival and 90-day diabetic reversal in rats. Finally, we demonstrate 1-month islet survival in a nonhuman primate without the need for immune suppression in the subcutaneous space. Collectively, these results indicate the device supports cell survival and function across multiple transplant models in three species without the need for any immunosuppression or external user intervention. These results represent an important set of advances towards immunosuppression free, minimally invasive islet transplantation.
    Keywords:  Bioelectronics; Cell Therapy; Diabetes; Islet Transplantation; Macroencapsulation; Oxygenation
    DOI:  https://doi.org/10.1016/j.device.2026.101084
  37. ACS Appl Mater Interfaces. 2026 May 25.
    Emerging Dynamic Polymers for Sustainable Materials.
    Lihao Yuan, Qi Zhang.
      Introducing dynamic chemical bonds into conventional polymers offers a chemical approach to sustainable materials, which is essential for future circular economy. Dynamers, i.e., dynamic polymers, have started to regain momentum with rising attention on plastic recycling, responsive, and sustainable materials in the past decade. This perspective aims at an overview of the historical milestones of dynamers as well as introducing the emerging chemical toolboxes for dynamic polymers by highlighting the state-of-the-art examples at the interfaces of dynamic covalent bonds, noncovalent bonds, and mechanical bonds. An outlook on existing challenges and future opportunities is provided to give insights into the possible future trajectory of this field.
    Keywords:  circular polymers; closed-loop recycling; dynamers; dynamic covalent bonds; sustainable materials
    DOI:  https://doi.org/10.1021/acsami.6c06751
  38. ACS Appl Mater Interfaces. 2026 May 29.
    Closed-Loop Recyclable, Tough, and Solvent-Resistant Electromagnetic Shielding Hydrogel Inspired by Dragonfly.
    Jingyi Kang, Meiming Lu, Yan Wang, Xin Liu, Qin Zhang.
      Electromagnetic shielding hydrogels have attracted much attention in stress sensing, motion monitoring, and bioelectronics. However, existing works mainly focus on improving electromagnetic shielding and sensing performance while ignoring the development of solvent resistance and material closed-loop recycling performance required for liquid-environment applications. In this work, a dragonfly-inspired solvent-resistant and closed-loop recyclable electromagnetic shielding hydrogel is successfully prepared via the biomimetic dual-network structure constructed by combining rigid polyimide (PI) with flexible poly(vinyl alcohol) (PVA). The electromagnetic shielding hydrogel features high mechanical strength and reprocessing and welding capabilities. More importantly, the hydrogels demonstrate closed-loop recycling of polyimide monomers and graphene nanofillers, and the recycled monomers and graphene can be reused in the construction of solvent-resistant electromagnetic-shielding hydrogels. Furthermore, electromagnetic shielding hydrogels are designed as stress sensors for monitoring strain and pressure signals, whether in air, water, or organic solvents. It is anticipated that the strategy of solvent-resistant and sustainable electromagnetic shielding hydrogels will provide a promising opportunity for various flexible electronics in liquid environments.
    Keywords:  closed-loop recycling; dragonfly inspire; electromagnetic shielding; hydrogel; solvent-resistance
    DOI:  https://doi.org/10.1021/acsami.6c06140
  39. Nat Commun. 2026 May 27.
    Enhanced volumetric additive manufacturing via Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerization.
    Eduards Krumins, Yaxuan Sun, Long Jiang, Vincenzo Taresco, Daniel J Keddie, Ricky D Wildman, Hayden Taylor, Derek J Irvine.
      Computed Axial Lithography (CAL), a Volumetric Additive Manufacturing (VAM) technology, enables the rapid, full body i.e. not layer-by-layer, fabrication of freeform geometries within seconds through the superposition of projected light patterns. However, as conventional CAL relies on free radical polymerization (FRP), it is an intrinsically exothermic process (ΔT > 60 °C) that can trigger auto-acceleration, so compromising print fidelity and limiting scalability. By regulating polymer chain length during propagation through reversible chain transfer, Reversible Addition-Fragmentation Chain Transfer (RAFT) maintains steady, controlled reaction kinetics and prevents the sharp viscosity increase characteristic of FRP. In this study, we introduce RAFT polymerization into various (meth)acrylate-based systems within CAL to effectively mitigate heat generation and suppress auto-acceleration during photopolymerization. The success of this approach is confirmed by in-situ thermal monitoring and the suppression of thermally induced buoyancy, revealing a substantial reduction in temperature rise compared to FRP. Furthermore, RAFT chemistry enables post-printing functionalization of the printed objects, expanding CAL's chemical versatility. This study demonstrates that RAFT-mediated CAL allows the fabrication of structures inaccessible via FRP, advancing thermally stable and functionally tunable volumetric additive manufacturing.
    DOI:  https://doi.org/10.1038/s41467-026-73456-8
  40. Adv Mater. 2026 May 26. e73495
    Digital Light Processing of Three-dimensional Liquid Metal Hydrogels.
    Junjie Du, Yuting Wang, Wenbo Zhao, Qinghe Cao, Yingyi Cui, Fan Bu, Cao Guan.
      Liquid metal (LM) hydrogels emerge as promising materials for flexible electronics and soft robotics, but they are challenged by simplistic structure, limited precision, and insufficient functional designability. Herein, we demonstrate the first digital light processing of three-dimensional (3D) LM hydrogels with micrometer precision (10 µm) and arbitrarily elaborated architectures. A universal strategy is developed for photo-curable LM-based various resins by encapsulation of LM droplets with sodium alginate (SA). The SA coating not only prevents the ink from sedimentation and self-polymerization by forming hydrogen and ionic bonds, but also ensures uniformly dispersed ink with maintained photo-curing properties. As a result, the photo-cured 3D LM hydrogels illustrate enhanced tensile stretchability (2000%) and cycling stability (800 cycles at 500% strain), which outperforms most previously reported 3D hydrogels. The 3D LM hydrogel also shows enhanced sensitivity and tunable photothermal responsivity, demonstrating promising applications in strain sensors, object grasping robotics, remote-controlled devices, and anti-counterfeiting systems.
    Keywords:  4D printing; digital light processing; liquid metal hydrogel; orthogonal encryption display; soft robot
    DOI:  https://doi.org/10.1002/adma.73495
  41. bioRxiv. 2026 May 12. pii: 2026.05.08.723928. [Epub ahead of print]
    AI-discovered protein fragments as generalizable regulators of biomolecular condensates.
    Andrew Savinov, Jibin Sadasivan, Kyle J White, Jack D Rubien, Gene-Wei Li, Lindsay B Case.
      Biomolecular condensates are a major driver of cellular organization; however, we lack a predictable and systematic approach to modulate the multivalent interactions underlying their formation. Here, we demonstrate that the AI-driven FragFold method enables robust and generalizable design of protein fragments to control biomolecular condensate formation. We apply this approach across diverse proteins: G3BP1, SARS-CoV-2 nucleocapsid, TDP-43, and focal adhesion kinase (FAK). Computationally screening 2,235 fragments, we selected 18 candidates for further investigation. Overall, we attain a 50% success rate (9/18 designs) in discovering condensate-controlling protein fragments, experimentally testing just 3-5 candidates per protein. For each condensate-forming protein, the success rate is at least 40%. Furthermore, FragFold-predicted fragment binding modes align with their condensate-inhibitory or -enhancing activities, revealing both known and newly identified interactions underlying condensate formation. In FAK, a condensate-inhibitory fragment uncovered a domain interaction required for phase separation, and mutational analysis validated its importance. Notably, this inhibitory fragment also suppresses FAK condensate formation in living mammalian cells. Together, these results establish AI-guided protein fragment discovery as a generalizable strategy to dissect and control the molecular interactions that govern biomolecular condensates.
    DOI:  https://doi.org/10.64898/2026.05.08.723928
  42. ACS Appl Mater Interfaces. 2026 May 28.
    Self-Strengthening of Force-Adaptive Hydrogels Cross-Linked with Pluronic Micelles through Mechanical Training.
    Rongze Gao, Yuxuan Zhu, Haojie Jin, Yujun Liu, Xu-Ming Xie.
      Hydrogels with excellent flexibility and stimulus responsiveness have important applications in flexible devices such as artificial muscles and soft robots. Various hydrogels can respond to thermal, electrical, and pH stimuli, while it remains challenging to fabricate force-adaptive hydrogels that can adapt to external mechanical stimuli to enhance their mechanical properties, mimicking the strengthening behavior of human muscles after physical training and exercising. Herein, a force-adaptive, self-strengthening poly(acrylic acid) (PAA) hydrogel was fabricated using block copolymer Pluronic F127 (PEO99-PPO65-PEO99) diacrylate and zirconium ions (Zr4+) as cross-linkers. The Pluronic F127 diacrylate (PF127DA) phase-separated and self-assembled into nanosized micelles in the hydrogels, and zirconium ions (Zr4+) formed metal coordination with the carboxyl groups in PAA, which endowed the hydrogels with high tensile strength and high stretchability. Notably, the mechanical properties of the hydrogels were significantly improved after the adequate cyclic stretch training and sufficient rest time. The tensile strength of the hydrogel increased from 1633 to 2463 kPa, and the elongation at break increased from 829% to 1026% after training at 500% strain and resting for 24 h. Small-angle X-ray scattering (SAXS) showed that the sizes of Pluronic micelles became smaller after training, and low-field nuclear magnetic resonance (LF-NMR) demonstrated a more homogeneous hydrogel network with a higher cross-linking density. During cyclic stretching, the nanosized Pluronic micelles separated and reconstructed into smaller micelles, generating additional cross-linking domains and accounting for a higher cross-linking density. The homogeneity of the hydrogel network also increased through the reconstruction of Pluronic micelles and the break recombination of the carboxyl-Zr4+ coordination cross-links, thereby improving the mechanical properties of the hydrogel through training significantly. This research presents an effective approach for developing hydrogels with high tensile strength, high toughness, and force-adaptive capabilities and shows potential to create self-strengthening hydrogels like muscles for future soft robots through mechanical training.
    Keywords:  force-adaptive; high strength; mechanical training; pluronic micelle; poly(acrylic acid) hydrogel; self-strengthening
    DOI:  https://doi.org/10.1021/acsami.6c04453
  43. Cell Stem Cell. 2026 May 29. pii: S1934-5909(26)00193-1. [Epub ahead of print]
    Evolving strategies for lineage tracing: Genetic markers, synthetic barcodes, and natural variants.
    Zhixin Kang, Hui Chen, Siyang Li, Shou-Wen Wang, Bin Zhou.
      Elucidating cell fate decision-making requires linking lineage history to dynamic phenotypic states. Driven by single-cell sequencing and genome engineering, lineage tracing has evolved from observational studies into a multidimensional, high-throughput discipline. Here, we synthesize its three methodological pillars: prospective tracking via genetic markers, high-throughput mapping using synthetic barcodes, and retrospective tracing leveraging endogenous natural variants. We survey their integration with multi-omics and spatial profiling, alongside computational approaches to decode cell fates from lineage data. By detailing each approach's trade-offs, we offer a systematic guide for experimental design and highlight emerging frontiers for translating precision clonal analysis into the clinic.
    Keywords:  barcoding; cell fate; development; diseases; lineage tracing; recombinase; regeneration
    DOI:  https://doi.org/10.1016/j.stem.2026.05.001
  44. Proc Natl Acad Sci U S A. 2026 Jun 02. 123(22): e2605176123
    Growth in confinement promotes Pseudomonas aeruginosa tolerance to antibiotics.
    Sourabh Monnappa, Zainebe Al-Mayyah, Mahmut Selman Sakar, Alexandre Persat.
      Bacteria often proliferate within confined spaces imposed by host tissues, extracellular matrices, or their own biofilms where cells press against surrounding materials and experience elevated mechanical stress. Whether these forces influence pathogen physiology and fitness remains unresolved. We show that Pseudomonas aeruginosa adapts to mechanical confinement by increasing resilience to antibiotics. Using synthetic hydrogels of tunable stiffness that restrict expansion without limiting nutrient access, we demonstrate that growth in elastic materials reduces P. aeruginosa sensitivity to antibiotics in a stiffness-dependent manner. Although slower growth contributes to tolerance, Tn-seq under colistin and tobramycin treatment identified key regulators of mechanically induced tolerance. We found that active efflux mediated by sodium-proton Sha antiporters, together with protective remodeling of the bacterial membrane, enhances the resilience of confined populations without impacting growth. These findings reveal that P. aeruginosa adapts to mechanical stress in ways that may promote treatment failure even in the absence of intrinsic resistance.
    Keywords:  Pseudomonas aeruginosa; antibiotic tolerance; confined environments; mechanobiology
    DOI:  https://doi.org/10.1073/pnas.2605176123
  45. ACS Appl Mater Interfaces. 2026 May 28.
    QuantGUV: Quantifying Encapsulation Efficiency of Small Molecules in Giant Unilamellar Vesicles.
    Zak Marshall, Reshma Bano, Pasha Dylan, Luisa Trifan, Callum Mckeaveney, André P Gerber, Wooli Bae.
      Synthetic cells, constructed through the self-assembly of small molecules, are designed to mimic life-like behaviors by encapsulating functional molecules. For such synthetic cells to accurately replicate cellular reactions, it is critical that the concentrations of encapsulated molecules mirror those in living systems, as reaction kinetics and cellular network states are highly sensitive to these concentrations. However, current methods for precisely determining encapsulation efficiency in synthetic cells at the single-cell resolution have been limited. To address this challenge, we present QuantGUV, a software-driven, image-based analysis method that determines the concentrations of fluorescent molecules encapsulated within giant unilamellar vesicles (GUVs). We use QuantGUV to measure the encapsulation efficiencies of three fluorescent molecules, sulforhodamine B, mEGFP, and polystyrene beads for GUVs formed via the water-in-oil emulsion transfer method. The encapsulation efficiencies for polystyrene beads were close to 100% in most of the conditions, while sulforhodamine B and mEGFP's encapsulation efficiencies depended on the parameters during GUV formation, such as concentrations of lipids and oil-water ratio during GUV formation. By providing crucial insights into encapsulation efficiencies, QuantGUV offers a valuable tool to support the construction of quantitative synthetic cell systems with accurately controlled internal environments.
    Keywords:  confocal microscopy; encapsulation efficiency; giant unilamellar vesicles (GUVs); high-throughput; image analysis; quantGUV; synthetic cells
    DOI:  https://doi.org/10.1021/acsami.6c03651
  46. Sci Adv. 2026 May 29. 12(22): eaec2554
    De novo promoters emerge more readily from random DNA than from genomic DNA.
    Timothy Fuqua, Andreas Wagner.
      Promoters are DNA sequences that initiate transcription. We studied the propensity of both random and genomic DNA to initiate transcription. To this end, we assayed the promoter activity of 17,129 random, synthetic DNA sequences and 91,866 Escherichia coli genomic sequences. Genomic DNA encodes ~1.3× more promoters than random DNA. This higher incidence of promoters also holds for intragenic regions, suggesting an underappreciated role for intragenic promoters. We also explored the propensity of nonpromoter sequences to become promoters. To this end, we chose 225 random and 60 genomic sequences without promoter activity, created over half a million DNA mutants from them, and assayed these mutants for novel promoter activity. Promoters emerge ~3× more readily from random DNA than from genomic DNA, because the genome contains fewer proto-binding sites for transcriptional activators. Our work shows that the genome has a smaller evolutionary potential to create new transcripts than random DNA.
    DOI:  https://doi.org/10.1126/sciadv.aec2554
  47. Nat Biomed Eng. 2026 May 27.
    Cell-based cytokine patch for localized immunomodulation and accelerated healing in rodent and porcine wounds.
    Christian C Schreib, Elizabeth L Kelley, Gillian Audia, Raghav Garg, Scott Johnson, Samantha Fleury, Marissa N Behun, Dilrasbonu Vohidova, Mangesh Kulkarni, Grace M Donnell, Bryan N Brown, Stephen F Badylak, Tzahi Cohen-Karni, Omid Veiseh.
      Wounds can become chronic if the biological processes that coordinate tissue repair, including immune cell activity and matrix remodelling, become dysregulated. Current treatments mainly focus on a wound's physical properties, such as moisture and pressure, and do not restore the disrupted molecular pathways. Here we show a removable patch containing engineered human cells that continuously release native cytokines and that can accelerate healing in rodent and porcine full-thickness wounds. The patch is a polydimethylsiloxane structure that houses alginate-encapsulated human retinal epithelial cells engineered to secrete individual cytokines relevant to tissue repair. Once placed on the wound bed, the cells remain viable and locally release the cytokines over several days. Delivery of interleukin 10, interleukin 12 and transforming growth factor-beta accelerates wound healing in mice and pigs, with accompanying changes in gene expression linked to tissue repair, including pathways involved in skin development and collagen organization. This work suggests that localized, cell-based cytokine delivery may enable future wound treatments that directly modulate the cellular programs governing tissue repair.
    DOI:  https://doi.org/10.1038/s41551-026-01687-7
  48. Nature. 2026 May 27.
    Move over, AlphaFold: open-source model predicts shape of 1 billion proteins.
    Ewen Callaway, Miryam Naddaf.
      
    Keywords:  Biotechnology; Databases; Machine learning; Proteomics
    DOI:  https://doi.org/10.1038/d41586-026-01686-3
  49. Nat Biotechnol. 2026 May 26.
    Improving multimodal wearable sensing for healthcare with artificial intelligence.
    Yizhou Bian, Shichao Ding, Catherine R Jutzeler, Sheng Xu, Noé Brasier, Joseph Wang.
      
    DOI:  https://doi.org/10.1038/s41587-026-03134-z
  50. Proc Natl Acad Sci U S A. 2026 Jun 02. 123(22): e2531265123
    Tuning mitotic recombination with patterned DNA nicks for precision mosaic analysis.
    Yifan Shen, Ann T Yeung, Bei Wang, Chun-Ting Yeh, Payton Ditchfield, Elizabeth Korn, Chun Han.
      CRISPR/Cas9-based mosaic analysis is a powerful tool for in vivo genetics but is limited by cytotoxicity and mutagenesis associated with DNA double-strand breaks. Here, we establish Cas9-derived nickases as safer and more reliable alternatives for inducing mitotic recombination in Drosophila. We demonstrate that single-strand nicks are sufficient to generate mosaic clones and systematically dissect the parameters governing this process. We find that clone frequency can be controlled by the gRNA nicking pattern, with two distant nicks on the same DNA strand synergistically enhancing recombination by over ninefold compared to a single nick. Based on these findings, we propose a mechanistic model for nick-induced crossover and provide a versatile toolkit for generating tissue-specific nickases. This work establishes nickase-based mosaic analysis by gRNA-induced crossing-over as a superior method for high-fidelity clonal analysis, enabling more precise investigation of gene function in development and disease.
    Keywords:  CRISPR; Drosophila; MAGIC; mosaic analysis; nickase
    DOI:  https://doi.org/10.1073/pnas.2531265123
  51. Food Res Int. 2026 Aug 31. pii: S0963-9969(26)01076-8. [Epub ahead of print]238 119399
    Single step fabrication of muscle bundles for cultivated meat using mechanotransduction: a paradigm shift.
    Jasmine Si Han Seah, Lay Poh Tan.
      Cultivated meat (CM) has emerged as a sustainable alternative to traditional livestock production however, commercialization remains constrained by several interconnected challenges, including the high costs of chemical differentiation media, and the complexity of multi-step scaffold-cell assembly processes. Cell expansion cost is an additional challenge that will be addressed by complementary efforts in the field. Here, we present a novel single-step, food-compatible wet-spinning platform that simultaneously integrates scaffold fabrication, stem cell encapsulation, and mechanotransducive stimulation, eliminating the need for exogenous soluble differentiation factors and post-fabrication cell seeding. This platform is fundamentally distinct from multi-step scaffold-cell assembly workflows reported in the literature, where scaffold fabrication, surface modification, cell seeding and biochemical myogenic differentiation induction are performed as sequential, independent operations. Using porcine adipose-derived stem cells (pADSCs) encapsulated within alginate-gelatin composite hydrogel microfibers, we demonstrate that scaffold stiffness and fabrication-induced shear stress alone are sufficient to drive myogenic progression toward terminal differentiation without any biochemical inducers. By harnessing mechanotransduction as the primary differentiation driver, this approach addresses key bottlenecks in CM manufacturing, including process simplification, cost reduction, and regulatory alignment through the use of food-safe, chemically defined materials. The resulting cultivated meat prototypes exhibited protein content, cooking behaviour, and textural properties approaching those of conventional pork loin. This work establishes a scalable, cost-efficient, and food-safe materials- and process-level framework for CM production driven by physical rather than biochemical cues.
    Keywords:  Alternative proteins; Cultivated meat; Mechanical compliance; Mechanotransduction; Scaffolds; Scalability
    DOI:  https://doi.org/10.1016/j.foodres.2026.119399
  52. Nat Commun. 2026 May 29.
    Metabolic feedbacks drive population dynamics and can lead to oscillations among leaf bacteria.
    Alan R Pacheco, Giovanni Stefano Ugolini, Simon H Rüdisser, Andrea Zamuner, Miriam Bortfeld-Miller, Patrick Kiefer, Franziska Oschmann, Samuel G V Charlton, Michael Berger, Tommaso Redaelli, Miguel Ángel Salazar, Ilija Dukovski, Jan Roelof van der Meer, Olga T Schubert, Martin Ackermann, Roman Stocker, Julia A Vorholt.
      Metabolic interactions are fundamental to the assembly and function of microbiomes. Yet, our understanding of how specific interaction mechanisms can drive broader ecological outcomes and population dynamics remains limited. Here, we monitor interactions resulting from plant oligosaccharide degradation by leaf-associated bacteria using a microfluidic device that enables direct cell observation and quantitative metabolite detection. This approach enables the identification of key metabolic mediators, revealing recipient-specific patterns of carbon substrate and cofactor complementation. By linking these patterns to emergent dynamics observed between pairs of bacteria, we identify metabolically driven feedbacks that could lead to a variety of ecological outcomes - from outcompetition to coexistence characterized by oscillating population abundances. Investigating these observations with metabolic modeling allows us to systematically assess the impact of specific molecular mediators on population dynamics, yielding predictions of interaction outcomes that we validate experimentally. Our results provide a detailed mapping of metabolic mechanisms to emergent population trajectories among environmental microbes and help inform strategies for designing microbiomes with desired steady states.
    DOI:  https://doi.org/10.1038/s41467-026-73686-w
  53. bioRxiv. 2026 May 16. pii: 2026.05.15.725600. [Epub ahead of print]
    PrEditR: A protein-centric platform for CRISPR-mediated base editor sgRNA design.
    Felipe Vasquez-Castro, Leonardo D Sanchez Solis, Samuel A Myers.
       Motivation: Post-translational modifications (PTMs) are critical to protein function, yet the function of most known modification sites remains uncharacterized. CRISPR-mediated phenotypic screens using base editors offer a powerful approach to dissecting PTM function at scale. However, existing sgRNA design tools for base editing applications are DNA-centric and lack the throughput required to integrate seamlessly with mass-spectrometry-based proteomics experimental outputs.
    Results: We introduce protein editing in R, PrEditR, an open-source, protein-centric tool for high-throughput sgRNA design for custom base editor screens. PrEditR enables users to designate specific amino acid residues in proteins and design protospacer sequences to target the endogenous gene to install missense mutations via base editors.
    Availability and Implementation: PrEditR is available on GitHub and Docker Hub.
    DOI:  https://doi.org/10.64898/2026.05.15.725600
  54. Nat Commun. 2026 May 28.
    A T7 RNAP regulatory toolbox for cell-free network engineering and biosensing applications.
    Pao-Wan Lee, Seyed Saeed Mottaghi, Matthis Guillaume Lugnier, Sebastian J Maerkl.
      T7 RNA polymerase is ubiquitously used in the fields of synthetic biology and biotechnology. Yet the ability to precisely and modularly regulate T7 RNAP remains surprisingly limited. Here, we engineer a T7 RNAP regulatory toolbox consisting of programmable synthetic repressors, activators, and biosensors in a cell-free system. This toolbox enables scalable design of T7 RNAP-based gene regulatory networks and enables rapid, sensitive, and multiplexed detection of diverse biomolecules, including small-molecule drugs, antibodies, and proteins, in a simple one-pot reaction. By integrating a protein design pipeline, we generate biosensors using fully synthetic binders, demonstrating the potential for rapid development of protein-based sensors. We construct a diagnostic cell-free system combining SARS-CoV-2 Spike protein sensing, gene regulatory based amplification, enzymatic amplification, and glucose based detection demonstrating the potential for point-of-care detection with high sensitivity. This work demonstrates a flexible and expandable framework for constructing gene circuits responsive to a wide range of biomolecules and demonstrates the potential for engineering point-of-care cell-free diagnostic assays.
    DOI:  https://doi.org/10.1038/s41467-026-73811-9
  55. bioRxiv. 2026 May 17. pii: 2026.05.14.725151. [Epub ahead of print]
    Counting to two: how phages decide between lysis and lysogeny.
    Janni Harju, Ghita Guessous, Zemer Gitai, Ned Wingreen.
      Upon infecting a bacterium, temperate phages must decide between killing the cell to reproduce (lysis) or entering a symbiotic lifestyle (lysogeny). This choice is often informed by the cell's state, as well as the number of infecting phage particles (MOI). Since phage gene copy numbers scale identically with MOI, an MOI-dependent decision requires a fast-acting asymmetry between the lytic and lysogenic pathways. We introduce a minimal model suggesting that only a handful of coupling mechanisms can produce such an asymmetry; for instance via a host protease, kinase, or RNase acting on one pathway. By distilling complex regulatory networks to their essential components, our model clarifies the logic of lysis-lysogeny decision mechanisms across phage species.
    DOI:  https://doi.org/10.64898/2026.05.14.725151
  56. ACS Appl Mater Interfaces. 2026 May 27.
    Fully Biobased, Robust, and High-Conductivity Hydrogel for High-Fidelity Electrophysiological Monitoring and Deep Learning-Assisted Stroke Rehabilitation.
    Zhoujing Chen, Didi Wen, Xiaoli Liang, Yuqi Li, Yongkang Bai.
      Developing sustainable bioelectronics that simultaneously integrate mechanical robustness, high conductivity, biocompatibility, and system-level functionality remains a fundamental challenge. Here, we report a Hofmeister-engineered, fully biobased hydrogel platform (GT2C20) that addresses these limitations through a synergistic dual physical cross-linking network. By combining citrate-induced chain compaction and continuous ionic transport pathways, this hydrogel achieves high tensile strength (0.73 MPa), large extensibility (272.5%), and high electrical conductivity (1.8 S m-1), overcoming intrinsic trade-offs in conventional gelatin-based systems. Building on these properties, GT2C20 enables an integrated multifunctional bioelectronic system. As a skin-conformal bioelectrode, it provides high-fidelity acquisition of electrophysiological signals (ECG, EEG, and EMG), achieving a high signal-to-noise ratio (24.3 dB for ECG) compared to commercial Ag/AgCl electrodes. When integrated with deep learning algorithms, the platform enables autonomous assessment of Brunnstrom stages for stroke rehabilitation with an accuracy of 97.31%, while a wireless telemedicine system supports remote diagnosis and personalized healthcare management. In parallel, the hydrogel functions as a highly stable strain sensor for real-time motion monitoring and precise gesture recognition, enabling intuitive control of prosthetic devices. Additionally, the hydrogel acts as a triboelectric nanogenerator electrode, yielding an open-circuit voltage of 72.1 V to power its own functions, while a microcontroller system supports wireless telemedicine and remote rehabilitation monitoring. This work presents an eco-friendly strategy for fabricating high-performance, biobased flexible electronics suited for health monitoring, telemedicine, and soft robotics.
    Keywords:  bioelectrode; green electronics; health monitoring; human−machine interaction; multifunctional hydrogel
    DOI:  https://doi.org/10.1021/acsami.6c03687
  57. ACS Environ Au. 2026 May 20. 6(3): 375-394
    Lignin-Based Hydrogels for Sustainable Agriculture: Extraction, Design, and Applications.
    Ankit Verma, Priyanka Devi, Sangeeta Bhogal, Rohit Jasrotia, Vijay Kumar Thakur.
      Synthetic polymers are widespread in modern life and pose growing environmental problems, especially in agriculture, where water management and soil health are crucial. Eco-friendly materials that balance performance and environmental safety are desperately needed as sustainable alternatives remain understudied. This study emphasizes the potential of lignin, a naturally occurring, abundant, and underutilized biopolymer, and its conversion into lignin-based hydrogels. Lignin hydrogels offer distinct benefits for agricultural applications due to their inherent antibacterial, biodegradable, and biocompatible properties. Their ability to swell improves soil water retention, promotes plant development in drought-prone areas, and permits regulated release of fertilizer. Lignin-based hydrogels can promote sustainable agricultural methods and lessen the dependency on synthetic polymers by customizing these characteristics. This study points to potential advances in green polymer technology by highlighting their capacity to bridge the gap between environmental stewardship and agricultural production.
    Keywords:  agricultural applications of hydrogels; extraction methods; extraction of lignin; lignin; lignin-based hydrogels; properties of hydrogels; structure of lignin; synthesis of hydrogels
    DOI:  https://doi.org/10.1021/acsenvironau.5c00203
  58. ACS Appl Mater Interfaces. 2026 May 29.
    Zwitterionic Powder-Based Gradient Adhesion-Lubrication Hydrogels for Efficient Hemostasis and Antiadhesion.
    Siyao Lv, Jinshuai Zhang, Ying Sun, Xiaoduo Zhao, Bo Yu, Zhengfeng Ma, Pengbin Yin, Shuanhong Ma, Feng Zhou.
      Uncontrolled hemorrhage, particularly from deep, irregular, and noncompressible wounds, remains a critical challenge in emergency medicine. Conventional hemostatic agents are frequently limited by poor sprayability, inadequate conformability to complex wound geometries, insufficient mechanical robustness, and lack of asymmetric adhesion properties. To address these limitations, we engineered a novel powder (CS-PSBMA@OHA) composed of zwitterionic poly(sulfobetaine methacrylate)-grafted chitosan (CS-PSBMA) and oxidized hyaluronic acid (OHA). Upon contact with moist tissue, the powder undergoes rapid liquid-triggered gelation, forming a stable, dual-network hydrogel. This architecture integrates a dense physical network, formed by strong intra- and interchain electrostatic interactions of zwitterionic PSBMA, with a dynamic chemical network established via Schiff base bonds with OHA. The resultant hydrogel adheres firmly to tissues by combining the rapid interfacial dehydration driven by zwitterionic PSBMA with the dynamic cross-linking enabled by OHA. This synergistic mechanism confers exceptional mechanical stability and sustained adhesion, even under dynamic fluid conditions. In both rat liver laceration and femoral artery transection models, CS-PSBMA@OHA demonstrated superior hemostatic efficacy, significantly reducing blood loss and hemostasis time compared to gauze and Yunnan Baiyao. Furthermore, the hydrogel exhibits a gradient adhesive interface: the tissue-contacting surface maintains strong adhesion, while the opposing side forms a hydrated lubrication layer. This asymmetric design effectively mitigates postoperative adhesions, as evidenced in a rat intestinal adhesion model. Collectively, this self-gelling powder-based platform represents a promising strategy for the development of multifunctional biomaterials that integrate rapid hemostasis with antiadhesive properties, offering potential clinical advantages in trauma and surgical settings.
    Keywords:  gradient hydration; hemostasis; liquid-triggered; postoperative antiadhesion; self-gelling
    DOI:  https://doi.org/10.1021/acsami.6c02828
This page is being maintained by Thomas Krichel. It was last updated on 2026‒05‒31 at 7:41.