bims-enlima 2026-05-17 papers

bims-enlima

Biomed News

on Engineered living materials

Issue of 2026–05–17
thirty papers selected by
Rahul Kumar, Tallinna Tehnikaülikool

Spore-Based Biocomposite Thermoplastic Polyesters with Enhanced Toughness and Programmable Disintegration.
3D-Bioprinted Marine Bacteria for the Degradation of Polyhydroxybutyrate Bioplastics.
Implantable living materials autonomously deliver therapeutics using contained engineered bacteria.
TridentSynth: a webtool for the retrosynthesis of molecules using chimeric type I polyketide synthases and chemoenzymatic pathways.
Vesicle-Templated Self-Assembly of Programmable Freestanding Multi-μm DNA Shells.
Synthesis of Programmable Bioelectronic Yeast for Biohybrid Futures.
Quantitative Measurement of Synthetic Repression Curves Reveals Design Challenges for Genetic Circuit Engineering under Growth Arrest.
A synthetic cell microreactor with two types of interacting dynamic DNA-based pores.
Cellular mechanometabolism: stimuli and implications.
Bioinspired ultrasound-driven ultrafast soft microgripper.
Mechanical force-induced tissue remodelling in a clinically relevant microphysiological model of asthmatic human lungs.
Scaffolds toughen bacteria-based therapy.
Strain stiffening and compression-induced softening of composite fibrous hydrogels derived from rod-shaped nanoparticles and a synthetic copolymer.
Temporal Programming of Cell-Free Transcription Using Orthogonal Enzyme-Responsive DNA Blockers.
Processing-Driven Control of the Properties of Polymer Grafted Nanoparticle Composites.
Controlling thermoreversibility and hole conductivity in thermoresponsive ionic biogels using phase morphology for neurohaptics.
Autonomous and Communicative Microcapsule Systems for Life-Like Homeostatic pH Regulation.
DNA-guided CRISPR-Cas12 for cellular RNA targeting.
A degradable PEGDA-dopamine hydrogel with ROS scavenging capacity supports flexible design for nerve repair.
Programmable nanobody circuits for cell selection.
Visible Light Photo-Cross-Linked Thermogel─A Single-Component Hybrid Supramolecular-Covalent Hydrogel for Sustained Drug Release.
Proton Conduction in Hydrogen-Bonded Networks Enables High-Speed PEDOT:PSS Devices.
Tunable PEG-Azlactone Hydrogels Enable Programmable Multiphase Drug Delivery.
A mismatch between slow protein synthesis and fast environmental fluctuations determines tradeoffs in bacterial proteome allocation strategies.
Galvanin (TMEM154) is an electric-field sensor for directed cell migration.
Epigenome regulators imbue a single eukaryotic promoter with diverse gene expression dynamics.
Cysteine-Derived Carbon Dots Hydrogels with Visible-Light-Driven Photocatalytic Therapy for Infected Wound Healing.
Electrodeposition-Optimized PEDOT Interfaces on Printed Circuit Boards for Stable, Low-Impedance Organoid Electrophysiology.
Time-temperature-transformation-layering diagrams: a design tool for lightweight multi-layered, single-material polymeric structures.
Cell cycle oscillations in a polarity network facilitate state switching by morphogenetic cues.

bioRxiv. 2026 Feb 26. pii: 2026.02.24.707801. [Epub ahead of print]

Spore-Based Biocomposite Thermoplastic Polyesters with Enhanced Toughness and Programmable Disintegration.

Han Sol Kim, Emily Fan, Arthi Chandra, Evangeline Meyler, Joanne Tang, Myung Hyun Noh, Adam M Feist, Jonathan K Pokorski.

Thermoplastic polyesters are widely used in commodity and high-performance applications due to their tunable and exceptional properties, versatile performance, and increasing relevance in sustainable materials. Integrating biological functionality into these polymers offers a promising route to enhance performance and end-of-life behavior beyond what conventional additives can achieve. Here, we report the generalization of an embedded spore-based engineered living material concept to three representative thermoplastic polyesters; polycaprolactone (PCL), polylactic acid (PLA), and poly(butylene adipate-co-terephthalate) (PBAT). Heat-shock-tolerized Bacillus subtilis spores were compounded with each polyester as a living biofiller via hot melt extrusion. The resulting biocomposite polyesters retained high spore viability (>90%) after extrusion and exhibited improved mechanical performance (up to 41% toughness improvement compared to neat polymers). End-of-life behavior was evaluated in a microbially-limited composting environment, where spore-containing PCL exhibited nearly complete disintegration within five months, corresponding to a ∼7-fold increase in degradation kinetics relative to neat PCL. Finally, 3D printing of biocomposite PCL was demonstrated through fused deposition modeling and direct ink writing methodologies. Together, this work demonstrated the successful extension of spore-based engineered living materials from thermoplastic polyurethane to multiple thermoplastic polyesters.

DOI: https://doi.org/10.64898/2026.02.24.707801
ACS Appl Polym Mater. 2026 May 08. 8(9): 6086-6100

3D-Bioprinted Marine Bacteria for the Degradation of Polyhydroxybutyrate Bioplastics.

Luying He, Hongyi Cai, Ram S Gona, Tiana C Rohe, Manasi Subhash Gangan, Timothy Lai, Diana R Sullivan, Meredith N Silberstein, Anne S Meyer.

  The severe, long-lasting harm caused by plastic pollution to marine ecosystems and coastal economies has led to the development of biodegradable plastics; however, their limited decomposition in marine environments remains a challenge. Here, technologies are presented for creating 3D-bioprinted living materials as a proof of concept for bioplastic degradation, with specific use in marine environments. The approach developed here integrates the halotolerant bioplastic-degrading bacterium Bacillus sp. NRRL B-14911 into alginate-based bio-ink to print an engineered living material (ELM) termed a "bio-sticker." Quantification of bacteria viability reveals that bioprinted marine bacteria survive within biostickers for more than 3 weeks. The rate at which the biostickers degrade the bioplastic polyhydroxybutyrate (PHB) can be tuned by altering biosticker biomass concentration, bioplastic concentration, or incubation temperature. Biostickers that are transferred to a different PHB sample still retain high biodegradation activity, demonstrating their reusability. Strain sweep oscillatory tests demonstrate that the biostickers display predominantly viscoelastic behavior. Monotonic tensile tests indicate that the elastic modulus and the adhesion of the biostickers are not negatively impacted by bacteria growth or incubation temperature. This work paves the way for the development of ELMs to facilitate the inclusion of bioplastics within the blue economy, promoting the emergence of more sustainable and eco-friendly materials.

Keywords:  3D bioprinting; biodegradable plastics; bioplastic-degrading bacteria; engineered living materials; marine debris

DOI:  https://doi.org/10.1021/acsapm.5c03370
Science. 2026 May 14. 392(6799): 729-734

Implantable living materials autonomously deliver therapeutics using contained engineered bacteria.

Tetsuhiro Harimoto, Fernando Herrero Quevedo, Janis Zillig, Sanjay Schreiber, Yi Wu, Christine Heera Ahn, Tania To, Rohan Thakur, Alexander M Tatara, Shawn Kang, Zheqi Chen, Nuria Lafuente-Gómez, Blake Hanan, Alexander Pauer, Shanda Lightbown, David A Weitz, David J Mooney.

Microbes are increasingly used as living therapeutics, yet their uncontrolled dissemination in the body has remained a clinical roadblock. Physical containment remains largely unattainable owing to eventual bacteria escape. In this work, we present an implantable material that encapsulates and confines bacteria, wherein synthetically engineered microbes produce therapeutic payloads from within. We developed a hydrogel scaffold with dual mechanical features: high stiffness to regulate bacterial proliferation and high toughness to resist material fracture under physiological stress. This design achieved complete bacterial containment for 6 months and withstood multiple forms of mechanical loading that otherwise caused catastrophic material failure. By genetically engineering embedded bacteria, we endowed the material with environmental sensing and on-demand therapeutic release capabilities and demonstrated autonomous treatment in a murine prosthetic joint infection model.

DOI: https://doi.org/10.1126/science.aec2071
Nucleic Acids Res. 2026 May 11. pii: gkag471. [Epub ahead of print]

TridentSynth: a webtool for the retrosynthesis of molecules using chimeric type I polyketide synthases and chemoenzymatic pathways.

Yash Chainani, Margaret Guilarte-Silva, Kenna Roberts, Stefan Pate, Geoffrey Bonnanzio, Keith E J Tyo, Aindrila Mukhopadhyay, Jay D Keasling, Hector Garcia Martin, Linda J Broadbelt, Tyler W H Backman.

The design of pathways to synthesize valuable molecules remains a central challenge in chemistry and biotechnology. Several computational retrosynthesis tools have been developed to address this problem, but their scope is often confined only to reactions in either synthetic organic chemistry or monofunctional enzymatic chemistry. We present TridentSynth, a web-based retrosynthesis tool (https://tridentsynth.lbl.gov) to scale synthesis planning up to three different routes by also incorporating multifunctional Type I polyketide synthase (PKS) enzymes into our reaction toolkit along with organic chemistry and monofunctional enzymes. Unlike monofunctional enzymes that catalyze single transformations, PKSs function as molecular assembly lines that catalyze multiple carbon-carbon bond formation reactions between acyl-coenzyme A substrates to construct elongated carbon scaffolds. PKSs follow a modular, programmable logic that allows them to be reconfigured to make new molecules in a predictable way. These scaffolds can then be chemoenzymatically modified to eventually access a wider array of molecular targets than would be possible with just synthetic chemistry or monofunctional enzymes alone, in a manner that mimics the evolved biosynthesis routes of many useful natural products. TridentSynth assists synthetic biologists by suggesting routes to synthesize a desired molecule through an intuitive web interface that requires no local installation or programming expertise.

DOI: https://doi.org/10.1093/nar/gkag471
Nano Lett. 2026 May 13.

Vesicle-Templated Self-Assembly of Programmable Freestanding Multi-μm DNA Shells.

Hao Yuan Yang, Christoph Karfusehr, Friedrich C Simmel.

  In the quest to create increasingly complex synthetic cell-mimicking systems, diverse DNA nanostructures have been developed to coat, permeabilize, sculpt, or otherwise functionalize lipid vesicles or used as scaffolds to direct vesicle growth. Here, we introduce a simple, broadly applicable method to realize freestanding, membrane-mimicking DNA shells: DNA shells are first assembled on giant unilamellar vesicles and then liberated by surfactant-mediated liposome removal, retaining the geometry of their membrane templates. We demonstrate this approach using two distinct DNA tecton classes: a complex barrel-shaped DNA origami and a simple 11-oligonucleotide nanostar-inspired motif. The site-specific addressability of DNA origami structures enables the rational design of binding interfaces, as demonstrated by the controlled formation of multilayer shells. The success of both strategies underscores the feasibility of using different DNA architectures to create tunable, DNA-only shell-like compartments spanning the size range of eukaryotic cells, thereby offering a fundamentally new type of compartmentalization for bottom-up synthetic biology.

Keywords:  DNA nanotechnology; compartmentalization; self-assembly; synthetic biology

DOI:  https://doi.org/10.1021/acs.nanolett.6c00402
Eng Biol. 2026 Jan-Dec;10:10 e70007

Synthesis of Programmable Bioelectronic Yeast for Biohybrid Futures.

Paige E Erpf, Bill D Kinder, Edward Archer, Roy S K Walker, Isak S Pretorius, Ian T Paulsen.

  The budding yeast Saccharomyces cerevisiae has moved beyond an evolved and domesticated single-celled microorganism into a deliberately engineered biological substrate. Advances in synthetic genomics, illustrated by the international Synthetic Yeast Genome (Sc2.0) project, have reframed the yeast genome as a designable and programmable system. This article examines how locus standardisation, genome refactoring, controlled genomic plasticity and orthogonal regulatory systems collectively establish yeast as a programmable platform. Yeast is then viewed as an analogue of electronic systems in which genetic circuits, memory and population-level computation are compared to logic gates, storage and distributed system architectures. These capabilities position yeast to move beyond conventional metabolic engineering towards hybrid systems that integrate biological information processing with electronic and computational components. Achieving such integration requires careful consideration of the interfaces between biological and electronic domains, including how biological states can be coupled to electronic systems through electrochemical, chemical, optical and mechanical transduction, and how electronic inputs can be delivered in forms that can be recognised and processed by engineered cells. Finally, both the principal bottlenecks and key enabling advances are discussed, highlighting how recent developments suggest that synthetic yeast is approaching readiness as a foundational platform for bioelectronic and hybrid living systems.

Keywords:  Sc2.0 chromosomes; bio‐design; genetic engineering; microbial engineering; synthetic biology

DOI:  https://doi.org/10.1049/enb2.70007
ACS Synth Biol. 2026 May 13.

Quantitative Measurement of Synthetic Repression Curves Reveals Design Challenges for Genetic Circuit Engineering under Growth Arrest.

John P Marken, Mark L Prator, Bruce A Hay, Richard M Murray.

  Despite the fact that microbes in natural environments spend most of their time in growth arrest, we understand little about how this physiological state affects the performance of engineered genetic circuits. Here, we measure repression curves from a library of genetic NOT gates at single-cell resolution in Escherichia coli under both active growth and growth arrest to systematically investigate how growth arrest affects circuit behavior. We find that the impact of growth arrest on circuit performance is almost entirely dominated by a >100-fold reduction in unrepressed expression levels. Growth arrest caused gene expression noise to increase only moderately and had minimal impact on the sensitivity and sharpness of the repression curves. Our work shows both that conventional genetic circuit design paradigms are currently insufficient to develop circuits that can function properly under growth arrest, and that addressing the reduction in just a single performance parameter would be sufficient to resolve this problem. This work expands our understanding of bacterial gene regulation under growth arrest and lays the groundwork for new design paradigms that will be essential to ensure the safe and reliable performance of synthetic biology systems in real-world environments.

Keywords:  gene regulation; genetic circuits; growth arrest; microbial physiology; synthetic biology

DOI:  https://doi.org/10.1021/acssynbio.6c00123
Nat Chem. 2026 May 15.

A synthetic cell microreactor with two types of interacting dynamic DNA-based pores.

Sisi Fan, Longjiang Ding, Benjamin Renz, Allen P Liu, Thomas Speck, Hao Yan, Stephan Nussberger, Na Liu.

Reconstructing cellular complexity is a central challenge in synthetic biology, with profound implications for understanding life and advancing bio-inspired nanotechnologies. A critical step towards this goal is replicating the dynamic interplay among membrane components and their functions. Here we demonstrate a double-necked synthetic cell microreactor (DCM) that incorporates two dynamic, DNA-based pores in the membrane of a giant unilamellar vesicle. The formation of the DCM leverages a signalling pathway mediated by giant unilamellar vesicle membrane dynamics to coordinate interactions between light-responsive small pores and self-arranged sealable large pores. This system enables sequential, on-demand delivery of molecular reactants with high spatiotemporal precision. Using DCMs, we demonstrate confined biochemical reactions, including a glucose oxidase-myoglobin cascade, cytoskeleton-mimetic actin polymerization and bundling, cell-free Spinach RNA transcription and the synthesis of three-dimensional DNA crystals that extend beyond natural systems. By coupling orchestrated multistep signalling with dynamic control of membrane permeability, the DCM establishes a versatile platform for emulating and expanding the functional complexity of natural cellular systems.

DOI: https://doi.org/10.1038/s41557-026-02124-7
EMBO Rep. 2026 May 09.

Cellular mechanometabolism: stimuli and implications.

Ismael Ortiz, Santiago Lopez, Raghu Vamsi Kondapaneni, Jose V Hernandez, Keefer Boone, Cynthia A Reinhart-King.

While much is known about the effects of the chemical microenvironment on cellular metabolism, mechanical cues have emerged as critical stimuli of intracellular metabolic pathways. Mechanical signals from the extracellular matrix (ECM), neighboring cells, and the microenvironment intersect with key regulators of cellular metabolism, often leading to changes in fundamental cell behaviors, including cell proliferation and migration. Here, we review recent work that has uncovered a role for mechanical cues from microenvironmental factors on cellular metabolism. We discuss how cell-ECM interactions and forces such as shear, tension, and compression affect cellular metabolic requirements and energy production. Importantly, mechanometabolism shapes both physiological homeostasis and pathological states, and further investigation has implications for understanding tissue function and disease progression and uncovering potential therapeutic strategies.

DOI: https://doi.org/10.1038/s44319-026-00795-4
Proc Natl Acad Sci U S A. 2026 May 19. 123(20): e2537655123

Bioinspired ultrasound-driven ultrafast soft microgripper.

Chengxi Zhong, Vincent Winderoll, Khemraj Gautam Kshetri, Cornel Dillinger, Tommaso Bianchi, Zhan Shi, Justus Schnermann, Marco Amabili, Song Liu, Raphael Wittkowski, Nitesh Nama, Daniel Ahmed.

  Understanding how acoustic waves interact with soft matter is critical for developing new strategies for dynamic control, actuation, sensors, and manipulation at small scales. A major challenge in soft matter and microrobotics is how to achieve fast, precise, and remotely controlled actuation at the microscale without sacrificing compliance or biocompatibility. Here, we introduce wireless artificial microcilia based on acoustically activated soft hydrogel microstructures inspired by Venus flytrap and vorticella. The structures, termed SonoGrippers, consist of dual microcilia (≤120 µm length) with outward-facing sharp tips. Upon acoustic excitation, SonoGrippers deliver ultrafast (~2 ms), reversible, and controllable actuation, enabling remote attraction, gripping, and release of objects. By tuning structural designs and acoustic parameters, SonoGrippers exhibit diverse deformation modes and tunable response dynamics, allowing adaptable gripping performance across various application scenarios. Proof-of-concept demonstrations with stationary and mobile biological samples confirm their robust functionality. Combining simple fabrication, additive-free operation, wireless rapid control, and biocompatibility, SonoGrippers provide a promising platform toward next-generation biomedical manipulation, soft microrobotics, and bioengineering applications.

Keywords:  bioinspired artificial microcilia; sound–soft matter interaction; ultrasound actuation

DOI:  https://doi.org/10.1073/pnas.2537655123
Nat Biomed Eng. 2026 May 11.

Mechanical force-induced tissue remodelling in a clinically relevant microphysiological model of asthmatic human lungs.

Jungwook Paek, Lakshminarayan Reddy Teegala, Farid Alisafaei, Anika Alim, Joseph W Song, Sunghee E Park, Jeehan Chang, Haijiao Liu, Bang-Jin Kim, Sandra Ryeom, Vivek Shenoy, Geremy C Clair, Charles Thodeti, Sailaja M Paruchuri, Dan Dongeun Huh.

Structural remodelling of living tissues due to mechanical forces is a common occurrence that plays an essential role in development, health and disease, but preclinical investigation of this dynamic process in human-relevant conditions remains a challenge. Here we present a microphysiological system integrated with pneumatically addressable soft actuators to emulate dynamic mechanical loading of mucosal tissues in the human respiratory tract. Using this system, we created a clinically relevant model of airway constriction in distal regions of asthmatic lungs to show compressive force-induced fibrotic airway remodelling. Following in vivo validation, we generated vascularized airway constructs in this model to investigate abnormal vascular remodelling in asthma, revealing airway constriction-induced subepithelial fibrosis as a key contributor to increased vascularity of asthmatic airways. Furthermore, we identified molecular mediators of abnormal airway remodelling through proteomics analysis of our microphysiological system and tested the feasibility of pharmacologically modulating their activity. We believe that our technology provides a useful tool for studying biophysical control and dysregulation of dynamic tissue remodelling in lungs and other mechanically active organs.

DOI: https://doi.org/10.1038/s41551-026-01669-9
Science. 2026 May 14. 392(6799): 690-691

Scaffolds toughen bacteria-based therapy.

Kaige Chen, Quanyin Hu.

Stiff, tough hydrogel layers that host bacteria enable sustained release of therapeutic molecules.

DOI: https://doi.org/10.1126/science.aeh1690
Mater Horiz. 2026 May 13.

Strain stiffening and compression-induced softening of composite fibrous hydrogels derived from rod-shaped nanoparticles and a synthetic copolymer.

Sofia Morozova, Yingshan Ma, Vahid Adibnia, Eugenia Kumacheva.

Biological fibrous networks exhibit a unique nonlinear response to deformation, that is, they stiffen under shear or elongational strains and soften under weak normal compression. Since these properties impact cell fate and may reflect pathological conditions, man-made fibrous gels can serve as an effective in vitro platform for studying the mechanical properties of biological tissues. Herein, we report an engineered fibrous hydrogel formed by the covalent crosslinking of rod-shape nanoparticles with a random copolymer. The variation in the copolymer composition led to a different degree of intrafibrillar crosslinking and broad-range variation in nonlinear mechanics of the hydrogel, which were not complemented by the change in gel structure. The hydrogel exhibited the properties of athermal enthalpic networks, in agreement with theoretical predictions. This work provides the ability to control nonlinear mechanical properties of fibrous hydrogels in disease modeling and in bioengineering.

DOI: https://doi.org/10.1039/d6mh00306k
ACS Synth Biol. 2026 May 15.

Temporal Programming of Cell-Free Transcription Using Orthogonal Enzyme-Responsive DNA Blockers.

Jordy Alexis Lerma-Escalera, Juliette Bucci, Ana Urošević, Romain Amador, Gianfranco Ercolani, Francesco Ricci.

  We report here the design of orthogonal, enzyme-driven DNA transcriptional timers that enable precise programming of time delays in cell-free in vitro transcription. These timers utilize blocker strands that transiently bind to the promoter domain, preventing transcription onset. Selective enzymatic cleavage of the blocker strands triggers their removal, allowing input DNA strands to bind and initiate transcription. By tuning the kinetics of enzymatic blocker degradation─through varying enzyme or blocker strand concentrations─we achieve fine temporal control over transcription half-life (t1/2) from 0.48 ± 0.02 h up to 8.4 ± 0.1 h. Using three different blocker-degrading enzymes (RNase H, uracil-DNA glycosylase (UDG), and formamidopyrimidine DNA glycosylase (Fpg)), we also demonstrate orthogonal temporal control of multiple transcription templates in a single solution. Finally, we show the programmed termination control and downstream regulation of Cas12a enzymatic collateral cleavage activity through such transcription timers. Together, these orthogonal DNA transcriptional timers establish a generalizable and straightforward framework for programming time-resolved transcription and gene expression in cell-free synthetic biology.

Keywords:  blockers; cell-free transcription; delay; enzyme; temporal control; timers

DOI:  https://doi.org/10.1021/acssynbio.6c00147
ACS Nano. 2026 May 12.

Processing-Driven Control of the Properties of Polymer Grafted Nanoparticle Composites.

Maninderjeet Singh, Huina Lin, Subhadeep Pal, Chaoqun Zhou, Masiuddin M Mohammed, Sri Maddukuri, Pablo Dean, Rongguan Yin, Michael R Bockstaller, Krzysztof Matyjaszewski, Zachary P Smith, Alamgir Karim, Jeffrey W Kysar, Sinan Keten, Brian C Benicewicz, Sanat K Kumar.

  The effect of preparation conditions on the properties of glassy polymers has been a subject of intense research, and these glassy polymers also age with deleterious consequences on properties. Here, we surprisingly find a similar preparation dependence for polymer-grafted nanoparticle melts (PGNP), even when the chains are in the melt. Specifically, we show that processing PGNPs by spin-casting vs slowly casting them from solutions yields temporally stable states with vastly different properties, including surface morphologies, mechanical properties, and gas transport. We propose that these differences arise because the end-grafted polymer brushes, especially for high grafting density and short chain lengths, are in an extremely long-lived colloidal glassy state, even though the chains themselves are mobile. Simulations suggest that there are strong variations in the chain interpenetration states between adjacent nanoparticles driven by solvent evaporation rates. With slower evaporation, there is evidently increased chain interpenetration leading to mechanical property improvements, while collapsed brushes dramatically increase gas permeability properties under fast evaporated conditions. These results strongly argue that processing protocols are an unappreciated control variable in determining the temporally stable properties of this class of materials.

Keywords:  mechanical properties; polymer brushes; polymer-grafted nanoparticles; structure−property relationship; topography

DOI:  https://doi.org/10.1021/acsnano.6c00412
Sci Adv. 2026 May 15. 12(20): eaee0777

Controlling thermoreversibility and hole conductivity in thermoresponsive ionic biogels using phase morphology for neurohaptics.

Ankan Dutta, Md Abu Sayeed Biswas, Ethan Gerhard, Mayukh Das, Long Meng, Wanqing Zhang, Wenjie Li, Arantza Moreno Calva, Shakul Pathak, Jia-Yu Yang, Junyi Yin, Jordan Meyet, Shuvendu Das, Bed Poudel, Abu Musa Abdullah, Yuju Che, Cheng-Hsin Chuang, Jian Yang, Sihong Wang, Xiaogang Hu, Saptarshi Das, Huanyu Cheng.

Integrating thermoreversibility with electrical conductivity in a unified hydrogel platform enables long-term, reusable through-hair neural interfaces. However, achieving both simultaneously remains challenging, as thermoreversibility demands network reorganization while conductivity necessitates network percolation. Here, we engineer phase morphology by controlling the components' viscoelastic state during mixing. Ionically conductive nucleated morphologies illustrated by liquid-liquid phase separation exhibit rapid thermoreversibility, whereas electrically conductive bicontinuous phases demonstrated by viscoelastic phase separation achieve a marginal gel-sol transition and an ultralow storage modulus of ~1.7 kilopascals while simultaneously achieving a conductivity of 7.5 siemens per centimeter or transconductance of 5.1 millisiemens in an organic electrochemical transistor. Below this threshold, systems resemble nucleated behavior, whereas above it, superior semiconducting properties emerge, but phase transition capability is lost. These materials enable reusable through-hair neural interfaces to maintain low skin contact impedance of 1.6 kohm·cm2 across different hair types for 3 days, facilitating stable event-related desynchronization detection during mechanical and electrical haptic sensation for personalized haptics.

DOI: https://doi.org/10.1126/sciadv.aee0777
Small. 2026 May 13. e73756

Autonomous and Communicative Microcapsule Systems for Life-Like Homeostatic pH Regulation.

Hongda Zhou, James Smith, Rui Cheng, Ramzan Ullah, Huaiyuan Wang, Dmitry Shchukin.

  Life sustains complex functions through intercellular communication networks that coordinate collective behavior and regulate environmental homeostasis. Replicating such dynamic and autonomous control over extended spatial and temporal domains in synthetic materials remains significant challenges. Here, we present a programmable dual-microcapsule system that emulates life-like homeostatic pH regulation via an antagonistic enzymatic network. The system integrates urease microcapsules (UMCs) and esterase microcapsules (EMCs), which were produced using microfluidic devices coupled with a surface co-assembly strategy. By integrating hybrid junction geometry with a modified epoxy post-coating strategy, the 3D-printed microfluidic device overcomes intrinsic structural defects and surface irregularities. The resulting amphiphobic and defect-free channels ensure stable droplet production and precise microsphere fabrication. Individual capsules display pH-mediated negative feedback through adaptive shell permeability, whereas mixed populations display communicate behaviors via pH signaling to generate programmable pH oscillations and feedback-controlled pH stabilization. This platform exhibits robust reaction to external pH control, long-term cycling stability, and inter-capsule interaction. This work offers a versatile route for engineering communicative, autonomous, and adaptive material systems, with broad implications for biomedical devices, environmental regulation, and soft control using chemical information exchange.

Keywords:  3D‐printed microfluidic; feedback; homeostasis; pH regulation; responsive microcapsule

DOI:  https://doi.org/10.1002/smll.73756
Nat Biotechnol. 2026 May 15.

DNA-guided CRISPR-Cas12 for cellular RNA targeting.

Carlos Orosco, Boyu Huang, Santosh R Rananaware, August P Bodin, Ivy Browning, Anne Fang, Michael P Baugh, Ian H Lange, Yasmin B Elhabashy, Mahika Balaraju, Jordan G Lewis, Nayan H Shah, Michael P Hanna, Sarah J Flannery, Katelyn S Meister, Vedant Karalkar, Piyush K Jain.

Here, we present ΨDNA, a DNA-based guide that enables RNA targeting by Cas12 nucleases, overcoming the traditional reliance on RNA-guided systems. We engineer ΨDNA to mimic a CRISPR RNA (crRNA) scaffold in reverse orientation, allowing AsCas12a and Cas12i1 to recognize RNA and trigger strong single-stranded DNA trans-cleavage for sensitive detection of diverse RNA species, including 100% accurate hepatitis C virus RNA detection in clinical samples. ΨDNA also achieves 70-95% multiplex knockdown of endogenous intracellular RNA transcripts through ribosome stalling across multiple human cell lines. Mechanistic studies reveal that activity depends on a stem loop that stabilizes a catalytically competent Cas12-ΨDNA-RNA complex. Lastly, codelivery of crRNA and ΨDNA enables simultaneous DNA editing and RNA knockdown with a single effector and modular fusions of different enzymes to AsCas12a extend ΨDNA to RNase H-mediated RNA degradation and METTL3-based epitranscriptomic editing. Together, ΨDNA guides constitute an adaptable toolkit that extends Cas12 systems beyond genome editing and diagnostics to enable precise, programmable control of cellular transcriptomes and their epitranscriptomic marks.

DOI: https://doi.org/10.1038/s41587-026-03129-w
Mater Today Bio. 2026 Jun;38 103203

A degradable PEGDA-dopamine hydrogel with ROS scavenging capacity supports flexible design for nerve repair.

Lin Huang, Ting-Yu Lu, Emma Berman, Alexander Park, Katarina Ercegovac, Jacob Schimelman, Shaochen Chen.

  Peripheral nerve injury remains a significant clinical challenge, with current therapeutic material limited by inadequate degradation control, insufficient oxidative stress management, and poor adaptability to patient-specific contexts. We developed a degradable poly (ethylene glycol) diacrylate-dopamine-acrylamide hydrogel platform that addresses these limitations, enabling tunable bulk degradation with concomitant dopamine release. By systematically varying the ratio of degradable crosslinker poly (ethylene glycol) diacrylate-dopamine, we generated composition-defined degradation profiles spanning 2 months with corresponding dopamine release patterns. The hydrogels exhibited mechanical properties comparable to native peripheral nerves while maintaining exceptional flexibility through multiple bending and torsional cycles. In vitro validation demonstrated that dopamine-releasing hydrogels effectively scavenged intracellular reactive oxygen species in both human Schwann cells and endothelial cells under oxidative challenge, while modulating Schwann cell gene expression in a pattern consistent with a transition from repair toward a pro-remyelination transcriptional profile, and shifting endothelial gene expression toward a pro-angiogenic transcriptional pattern. Using digital light processing bioprinting we fabricated customizable nerve wraps, tubular structures, and microarchitectures with internal channels that directed cell alignment, while controlled FITC-dextran release validated localized delivery capabilities. These findings establish a multifunctional hydrogel platform combining programmable degradation, antioxidant functionality, and cellular microenvironment control for peripheral nerve repair applications.

Keywords:  3D bioprinting; Biodegradation; Biomaterial; Peripheral nerve repair

DOI:  https://doi.org/10.1016/j.mtbio.2026.103203
bioRxiv. 2026 Feb 23. pii: 2026.02.22.707289. [Epub ahead of print]

Programmable nanobody circuits for cell selection.

Nathan B Wang, Albert Blanch-Asensio, Hannah Cevasco, Deon S Ploessl, Derin R Gumustop, Mary E Ehmann, Maria F Castellanos, Francisco J Sánchez-Rivera, Timothy M O'Shea, Kate E Galloway.

Efficient and scalable isolation of specific cell populations remains a central bottleneck for genome engineering, pooled screening, and cell therapy manufacturing. Here, we present DASIT ( D estabilized-nanobody A ntigen S election and I dentification T ool), a protein-based circuit for antigen-specific cell selection. DASIT uses a destabilized nanobody fused to an antibiotic resistance protein. In cells expressing the target antigen, binding of the nanobody fusion to the cognate antigen stabilizes DASIT, thereby coupling the presence of an antigen to a selectable signal. We developed DASIT circuits that enable robust selection of antigen-expressing cells and show that they can be designed to target distinct antigen classes and perform across cell types. Because DASIT operates at the protein level, it supports both stable integration and transient delivery, enabling recyclable selection without permanent genomic integration of resistance markers. We demonstrate scalable, FACS-free enrichment in three challenging applications: multiplexed, logic-gated integration of landing pads in human iPSCs, high-throughput CRISPR screening, and phenotypic selection of in vitro -derived neurons at transplantation scale. By decoupling selection from vector integration, DASIT establishes an automation-compatible architecture for multistep genome engineering, high-throughput library screening, and large-scale cell manufacturing.
Highlights: DASIT enriches for antigen-positive cells across multiple selection markers and antigensIntermediate levels of DASIT expression support selection across stable and transient delivery modalitiesLogic-gated, precision genome engineering of human iPSCs via DASIT selectionDASIT enables scalable activity-based selection for high-throughput base editing screensDASIT-selected engineered motor neurons survive grafting into acute spinal cord injury.

DOI: https://doi.org/10.64898/2026.02.22.707289
ACS Appl Mater Interfaces. 2026 May 14.

Visible Light Photo-Cross-Linked Thermogel─A Single-Component Hybrid Supramolecular-Covalent Hydrogel for Sustained Drug Release.

Qianyu Lin, Xin Yi Oh, Cally Owh, Belynn Sim, Valerie Ow, Joey Hui Min Wong, Yi Jian Boo, Nicholas Wei Xun Ong, Vinh Xuan Truong, Xian Jun Loh, Jason Y C Lim.

  Temperature-responsive supramolecular thermogels, advanced biomaterials that exhibit sol-to-gel phase transitions when warmed, show great promise as next-generation in vivo drug delivery depots for their excellent biocompatibility and ease of formulation and administration. However, the lack of permanent covalent cross-links within the gel framework often results in short in vivo persistence and rapid gel swelling, in turn limiting duration of sustained drug release attainable. Herein, we developed a general strategy that retains the thermogels' intrinsic ease of injectability, yet allowing significantly enhanced sustained drug release durations. By incorporating a visible light-cross-linkable chromophore into the thermogel polymer structure, in situ cross-linking can be achieved after depot administration with facile external control. As compared to conventional photo-cross-linking strategies utilizing ionizing and hazardous UV light, our thermogels can be covalently cured using blue light or even under ambient indoor lighting conditions, making them potentially suitable for sensitive applications such as ophthalmic drug release. We show that these thermogels can be applied as an in situ cross-linked depot that allows the release of the antivascular endothelial growth factor biologic, Aflibercept, to be prolonged for more than 3 months, achieving a marked improvement over existing treatment regimens for diseases such as neovascular age-related macular degeneration that necessitate monthly injections. Additionally, these photo-cross-linked thermogels can also prolong the release of small proteins (e.g., bovine serum albumin) from membrane-based delivery systems by more than 3 times compared to nonirradiated controls. These visible light-photo-cross-linkable gels offer new versatile platforms for achieving long-duration drug release suitable for different biological applications and delivery modalities.

Keywords:  biomaterials; chromophore; dimerization; injectable; sustained drug delivery; temperature-responsive hydrogel

DOI:  https://doi.org/10.1021/acsami.6c01197
ACS Appl Mater Interfaces. 2026 May 12.

Proton Conduction in Hydrogen-Bonded Networks Enables High-Speed PEDOT:PSS Devices.

Kalee Rozylowicz, Tyler Quill, Arianna Magni, Garrett LeCroy, Alberto Salleo.

  The speed of organic mixed ionic-electronic conductors (OMIECs) is often attributed to ion size and diffusivity, yet many devices display kinetics that far exceed expectations. Here, we identify proton transport as the fundamental switching mechanism in PEDOT:PSS electrochemical random-access memories (ECRAMs) and demonstrate how ionic liquid chemistry dictates this process. Using isotope substitution, we show that fast kinetics arise from cooperative proton hopping through extended hydrogen-bond networks, and that the 2-position proton of the imidazolium ring plays a decisive role in conduction. Alkylation suppresses transport by limiting water uptake, while imidazole doping restores hydrogen-bond connectivity under rigorously anhydrous conditions, eliminating the reliance on trace water for ultrafast switching. By establishing how subtle molecular features of ionic liquids control proton conduction, this work provides a mechanistic basis for the anomalous speed of OMIEC devices and outlines a molecular design strategy for high-speed neuromorphic and electrochemical technologies.

Keywords:  PEDOT:PSS; artificial synapses; ionic liquids; neuromorphic computing; organic mixed ionic−electronic conductors; organic semiconductors; proton hopping

DOI:  https://doi.org/10.1021/acsami.6c01801
Biomacromolecules. 2026 May 13.

Tunable PEG-Azlactone Hydrogels Enable Programmable Multiphase Drug Delivery.

Emily Rasmussen, S K Arif Mohammad, Kendall Kelly, Ally Grace Bounds, Kenneth Hulugalla, Penelope Jankoski, Evan Stacy, William L Jarrett, Tristan Clemons, Adam E Smith, Thomas A Werfel.

New therapeutic regimens increasingly rely on coordinated, time-dependent delivery of multiple agents, placing new demands on biomaterials capable of precisely regulating release profiles. In this work, azlactone-functional polymers were cross-linked with poly(ethylene glycol) (PEG) to create a tunable hydrogel platform in which cross-linking density and PEG-diol to PEG-diamine ratio (PEG-OH:PEG-NH) regulate network stability, hydrolytic degradation, and release kinetics. Herein, we evaluate how hydrogel composition influences network characteristics, degradation behavior, and the release of structurally diverse cargos, including small molecules, proteins, and nanoparticles. Across formulations, increasing PEG-OH:PEG-NH accelerated hydrolytic degradation, while decreasing cross-linking density expanded the initial mesh, together leading to differences in release kinetics. These programmable relationships enabled phased, multicargo release of small molecules and antibodies from the same hydrogel. Together, these findings highlight PEG-azlactone hydrogels as a promising platform for programmable, phased delivery of diverse therapeutic cargos.

DOI: https://doi.org/10.1021/acs.biomac.6c00138
bioRxiv. 2025 Jul 22. pii: 2025.07.22.666192. [Epub ahead of print]

A mismatch between slow protein synthesis and fast environmental fluctuations determines tradeoffs in bacterial proteome allocation strategies.

Leron Perez, Jonas Cremer.

Microbes live in environments that fluctuate faster than they can adjust their cellular machinery. To survive these fluctuations, they must dynamically regulate protein synthesis-a resource-intensive process that is often slower than environmental changes. Here, we develop a mechanistic model coupling antibiotic kinetics with dynamic proteome allocation to understand how limitations in translational capacity shape acclimation strategies. Using translation-inhibiting antibiotics and resistance proteins, we show that the temporal mismatch between environmental perturbations (seconds) and protein synthesis responses (hours) creates a growth advantage for anticipatory strategies where cells pre-synthesize resistance proteins before antibiotic exposure. Further, we find that the largest benefits of anticipation and the largest protein fractions reserved for anticipation are realized in environments with multiple antibiotics, suggesting that anticipation is most important in complex environments. This work establishes a framework for quantifying the costs and benefits of various acclimation strategies in dynamical environments based on the fundamental constraints of protein synthesis, with implications for microbial ecology, antibiotic resistance, and biotechnology applications.

DOI: https://doi.org/10.1101/2025.07.22.666192
Cell. 2026 May 12. pii: S0092-8674(26)00461-7. [Epub ahead of print]

Galvanin (TMEM154) is an electric-field sensor for directed cell migration.

Nathan M Belliveau, Matthew J Footer, Amy Platenkamp, Celeste Rodriguez, Heonsu Kim, Christopher K Prinz, Aaron P van Loon, Yubin Lin, Tara E Eustis, Michelle M Chan, Daniel J Cohen, Julie A Theriot.

  Directed migration of immune and epithelial cells is critical for rapid responses to tissue injury or infection. Endogenous electric fields, generated by disruption of the transepithelial potential across the skin, are thought to guide cells to wound sites. However, how single cells detect these electrical cues remains unclear. We identified Galvanin (TMEM154), a poorly characterized single-pass transmembrane protein, as required for electric-field-guided migration of rapidly moving cells. Expression of Galvanin is sufficient to confer electric-field-guided migration on otherwise non-responsive epithelial cells. Upon electric-field exposure, Galvanin rapidly relocalizes to the anodal side of cells, and in human neutrophils, relocalization is immediately followed by changes in spatial patterns of cellular protrusion and retraction. These data suggest Galvanin acts as a direct sensor of the electric field, transducing spatial information about a cell's electrical environment to the intracellular migratory apparatus to support directed cell migration.

Keywords:  CRISPR screen; Galvanin; TMEM154; biophysics; cell biology; directed cell migration; electrotaxis; functional genomics; galvanotaxis; neutrophils

DOI:  https://doi.org/10.1016/j.cell.2026.04.026
iScience. 2026 May 15. 29(5): 115805

Epigenome regulators imbue a single eukaryotic promoter with diverse gene expression dynamics.

Jessica B Lee, Leandra M Caywood, Riley Basinger, Lucas Abbott, Nicholas Levering, Albert J Keung.

  Biological information can be encoded in signaling dynamics, which have been implicated in many physiological processes; yet the diversity of dynamic expression profiles driven by a single gene remains unclear. To explore this, we screen 80 chromatin-associated proteins (CAPs) for their potential to drive diverse dynamic gene expression profiles from the same genome-integrated reporter in yeast. Using locus-specific optogenetic recruitment and live-cell microscopy, we measure dynamic expression profiles within single cells. CAP recruitment elicits a range of responses varying in activation delay, strength, production rate, and noise. We find that promoter activity is characterized by graded, rather than switch-like, transitions. A kinetic model with three promoter states and a positive feedback loop successfully captures the key features of expression driven by each CAP. These results reveal the rich dynamic landscape possible from a single gene, offering insights into native cellular processes and enhancing gene expression control in synthetic biology.

Keywords:  bioinformatics; biological sciences; evolutionary biology; natural sciences; synthetic biology

DOI:  https://doi.org/10.1016/j.isci.2026.115805
ACS Appl Mater Interfaces. 2026 May 11.

Cysteine-Derived Carbon Dots Hydrogels with Visible-Light-Driven Photocatalytic Therapy for Infected Wound Healing.

Huanxuan Huang, Chenyu Zhang, Dong Zhang, Hanwen Jiang, Keqing Xu, Shiyang Liao, Meidong Lang.

  The escalating crisis of multidrug resistance and biofilm recalcitrance poses severe challenges to conventional wound management. Photocatalytic antimicrobial therapy (PCAT) represents a promising nonantibiotic alternative that triggers the generation of reactive oxygen species (ROS) under illumination, thereby achieving broad-spectrum sterilization. Herein, we engineered a metal-free, visible-light-driven photocatalyst based on cysteine-derived carbon dots (Cys-CDs) via a facile microwave-assisted approach. Through precise N, S-heteroatom doping, the Cys-CDs possess tailored bandgaps of 2.78 eV, conferring them with superior visible-light harvesting capability. Upon visible-light exposure, the photocatalytic generation of ROS drives potent antibacterial efficacy, achieving >95% bacterial eradication against Staphylococcus aureus at 31.25 μg/mL and Escherichia coli at 62.5 μg/mL. Importantly, the unique ROS-mediated antibacterial mechanism of Cys-CDs induces nonspecific oxidative damage to bacterial components, thereby fundamentally circumventing the evolution of resistance. Subsequently, Cys-CDs were covalently integrated into an alginate hydrogel matrix to construct a sustained-release platform (CCDs/SA). The resultant hydrogel retains robust photocatalytic antibacterial activity, demonstrating excellent performance in inhibiting biofilm formation and eradicating mature biofilms. Notably, the CCDs/SA hydrogel exerts selective bactericidal activity through differential enzymatic modulation, effectively eliminating bacteria while simultaneously promoting mammalian cell proliferation and migration. In an infected full-thickness skin wound model, the hydrogel combined with visible-light irradiation achieved near-complete bacterial eradication (99.07%) by day 7 and accelerated wound closure to 97.35% within 14 days, significantly outperforming commercial antibacterial dressings. Collectively, this work establishes a nonantibiotic therapeutic strategy for engineering visible-light-driven platforms, holding great promise for the clinical management of infected wounds.

Keywords:  antibacterial; carbon dots; hydrogel; photocatalytic effect; wound healing

DOI:  https://doi.org/10.1021/acsami.6c05260
ACS Appl Mater Interfaces. 2026 May 11.

Electrodeposition-Optimized PEDOT Interfaces on Printed Circuit Boards for Stable, Low-Impedance Organoid Electrophysiology.

Sara Ebrahimi, Sabra Rostami, Gayaneh Petrossian, Eric Quenneville, Noemie-Manuelle Dorval-Courchesne, Christopher Moraes, Fabio Cicoira.

  Reliabl electrophysiological sensing in brain organoids is limited by the high interfacial impedance and noise of microscale electrodes, particularly when scalable and reusable platforms are required. In this work, we introduce PEDOT-coated printed circuit board (PCB) electrodes as a biosensing platform for low-noise recording of organoid electrical activity. Conducting polymer coatings were electrodeposited directly onto PCB-integrated electrodes and systematically optimized to maximize interfacial capacitance while preserving coating adhesion and durability. The optimized PEDOT interfaces reduced electrode impedance to 3-5 kΩ at 1 kHz, corresponding to about three-order-of-magnitude decrease compared to Au-coated electrodes. The low-impedance response was retained after repeated autoclave sterilization and sonication, demonstrating robustness under conditions relevant to routine biological use. When applied to human brain organoids, the PEDOT-coated electrodes exhibited markedly reduced background noise and significantly enhanced signal-to-noise ratios (SNR), enabling reliable detection of extracellular spikes and synchronized burst activity across multiple channels. Relative to gold electrodes, the PEDOT-modified PCB platform recorded higher-amplitude signals and increased spike counts, indicating improved electrode-tissue coupling. These results establish PEDOT-coated PCB electrodes as a scalable and reusable biosensing interface for electrophysiological interrogation of 3D neural tissues.

Keywords:  PCB; PEDOT; bioelectronic interfaces; electrophysiology; low-impedance electrodes; midbrain organoids

DOI:  https://doi.org/10.1021/acsami.6c03097
Mater Horiz. 2026 May 12.

Time-temperature-transformation-layering diagrams: a design tool for lightweight multi-layered, single-material polymeric structures.

Emilia Di Lorenzo, Lorenzo Miele, Alessandra Longo, Ernesto Di Maio, Maria Laura Di Lorenzo.

In the design for recycling strategy, reducing the number of different materials is encouraged. However, multi-material structures like multi-layers are often used to optimize performance. Here, we demonstrate that, by engineering the coupled mass and heat transport during the processing of semi-crystalline polymeric components, it is possible to achieve a multilayered structure using a single material. Layering-in terms of crystallinity and foaming-has been accomplished by identifying the processing window in which the characteristic times are of the same order of magnitude for (i) mass transport of the foaming agent, (ii) heat transport and (iii) polymer crystallization. A time-temperature-transformation-layering diagram is thus constructed and exploited. This strategy has been validated using two different semi-crystalline polymers, poly(lactic acid) and poly(ethylene terephthalate), and CO2 as a foaming agent. We demonstrate that sustainability and performance need not be mutually exclusive. Possibility of leveraging this approach with other types of materials and/or processes for which layering is required significantly broadens the scope of this research.

DOI: https://doi.org/10.1039/d6mh00281a
Sci Adv. 2026 May 15. 12(20): eaec3379

Cell cycle oscillations in a polarity network facilitate state switching by morphogenetic cues.

KangBo Ng, Hadjar Sebaa, Nisha Hirani, Alex Chizh, Zeno Messi, Tom Bland, Kenji Sugioka, Nathan W Goehring.

The establishment of cell form, fate, and function during morphogenesis requires coordination between cell polarity and developmental cues. To achieve this, cells must establish polarity domains that are stable yet sensitive to guiding cues. Here, we show that Caenorhabditis elegans germline blastomeres use a time-varying polarization landscape to resolve this trade-off. Specifically, coupling the PAR polarity network to the oscillatory activity of cell cycle kinase CDK-1 ensures that newborn cells operate in a low feedback regime that lowers barriers to state switching, allowing spatial cues to induce and orient PAR protein asymmetries. As CDK-1 activity rises during mitosis, molecular feedback increases, reinforcing cue-induced asymmetries to yield robust and stable patterning of PAR polarity domains. Consistent with this model, we show that low CDK/feedback regimes destabilize PAR domains but are required for de novo polarization and polarity reorientation by cues. We propose that oscillatory networks represent a general mechanism for dynamically optimizing cellular decision-making landscapes, ensuring robust, signal-induced state switching during development.

DOI: https://doi.org/10.1126/sciadv.aec3379