bims-enlima 2026-03-22 papers

bims-enlima

Biomed News

on Engineered living materials

Issue of 2026–03–22
37 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool

4D printing of fully programmable sheets of digital metamaterials.
Micropatterned DNA Hydrogels for Spatiotemporal Programming of Chemical Reaction Networks.
Synthetic aptamer mechanoreceptors enable cell-specific force sensing and temporal control via DNA circuits.
Synthetic circuits for cell ratio control.
Reprogrammable 4D tissue engineering hydrogel scaffold via reversible ion printing.
Modular noncovalent functionalization of electrospun piezoelectric scaffolds with bioactive nanocarriers.
Bioelectronic synthesis of hydrogen sulfide enables spatiotemporal regulation of protein modification and cellular redox.
Multiphasic droplet microfluidics platform for controlled bacteria and mammalian cell co-culture.
Automated Assembly of Programmable RNA-Based Sensors.
Light-Mediated Synthesis of Degradable Polymers With Complex Architectures Using α-Lipoic Acid as a Cleavable Comonomer.
A universal surface functionalization technique to chemically enhance live microbial cells.
Orthogonal Tri-Modular Coiled-Coil Assembly for Programmable Multi-Cargo Display on Escherichia coli Nissle 1917.
Design Strategies for Advanced Biomaterials Functionalized with Bioactive Peptides.
A DNA-encoded recipe to direct multistage colloidal assembly.
Thermoresponsive Gels Based on Cross-Linked Polymer-Grafted Cellulose Nanocrystals.
Transiently amplified fluctuations assemble dissipative materials.
Light-Driven C4 Biosynthesis from CO2 and H2O via Engineered Photocatalyst-Microbial Consortia.
Engineering ECM-mimetic scaffolds from biological macromolecules for physiologically relevant tumoroid models.
Dual-Pathway Strategy for Click-Type Functionalization and Programmable Polymer Deconstruction.
Nonmonotonic rate-dependent adhesion of hydrogels.
Mixed ionic-electronic conducting eutectic soft materials for bioelectronics.
Orthogonal quorum sensing circuits enable dynamic regulation in Escherichia coli.
Magnetic coupling transforms random snapping into ordered sequences in soft metamaterials.
Precise and Parallel Fabrication of Microactuator Arrays via Interfacial Supramolecular Adhesion.
Cellular Snowballing: Cell Adhesion and Migration Drive the Self-Assembly of Cell-Microgel Biohybrid Spheroids.
Engineering synthetic cells with intramembrane domains possessing distinct bilayer asymmetries.
Volumetric 3D printing of a fluoropolymer and closed-loop chemical recycling of its fluorinated content.
Manufacturing Silk Fibroin Hollow Nanoyarns as Fundamental Units for Advanced Medical Textiles.
Crosslinked ionizable lipids reprogram dendritic cell metabolism for potent mRNA vaccination.
Protein overabundance is driven by growth robustness.
Autonomous Synthesis and Scrambling of Phospholipids, Linked to Recycling of Cofactors in Synthetic Cells.
Microembossing Hydrogel Meso-Circuits for Patterning Dissociated Neurons Promotes Ensemble Formation.
Establishing direct relationships between soft material perception and rheology.
Photoclickable Halotag ligands for spatiotemporal multiplexed protein labeling on living cells.
Chemical Functionalization of 2D Materials.
Reprogrammed SimCells for antimicrobial therapy.
Precise, minimally evolved adenine base editors generated through mutation reversion analysis.

Soft Matter. 2026 Mar 16.

4D printing of fully programmable sheets of digital metamaterials.

Ido Levin, Ela Sachyani, Rama Lieberman, Noa Trink, Eran Sharon, Shlomo Magdassi.

Advances in 3D printing technology now enable the precise positioning of microscopic material voxels to form complex structures. Combined with emerging multi-material capabilities and printable responsive materials, this opens new possibilities for digital composite materials and 3D printing of shape-transforming structures, a process known as 4D printing. Building upon these advancements, we present a novel methodology for designing and fabricating digitized 4D-printed shape-transforming sheets. We 3D print responsive continuous sheets composed of two layers, each consisting of active and passive voxels meticulously positioned to form thin structures that transform on demand. Our approach addresses a long-standing challenge in the field: the independent and simultaneous programming of lateral geometry and intrinsic curvature. This unprecedented control over the resulting shape unlocks new opportunities in synthetic shape-morphing materials. We provide a general algorithmic approach that is material-agnostic and enables systematic design of shape transformations with potential capabilities for programmable mechanical properties and multi-actuation-mode systems and applications in soft robotics and deployable structures.

DOI: https://doi.org/10.1039/d5sm00780a
ACS Nano. 2026 Mar 14.

Micropatterned DNA Hydrogels for Spatiotemporal Programming of Chemical Reaction Networks.

Kohei Nishiyama, Piet J M Swinkels, Brigitta Dúzs, Weixiang Chen, Andreas Walther.

  Cells in living systems communicate by sending and receiving signal molecules to coordinate their behavior. To achieve long-distance and noise-resistant communication, cells pattern themselves into spatially organized structures. Inspired by this strategy, systems biology and materials science have aimed to construct artificial communication systems whose dynamics can be controlled by their spatial arrangement. However, experimental understanding of how spatial arrangement influences communication remains limited, mainly due to the difficulty of precisely positioning multiple artificial cellular agents. Here, we demonstrate that communication between artificial cell-like units can be programmed using DNA-based reaction networks and tuned by their spatial arrangement. Arrays of DNA-functionalized hydrogel posts were fabricated as artificial cellular units using a microscale 3D printing technique, enabling precise and flexible control over their geometry and arrangement. The communication between the posts and the collective behavior of the array can be rationally programmed by implementing DNA-based chemical reaction networks. The arrays can sense locally added DNA stimuli and exhibit transient activation patterns that are unique to input positions. This concept is further extended to post-to-post communication, where catalytic signal amplification in a spatially separated configuration leads to spatially biased activation. Finally, by introducing a negative feedback loop between two post types, we achieve more complex spatiotemporal dynamics in which the collective behavior is strongly influenced by spatial arrangement. Our system provides a simple yet versatile experimental platform for exploring arrangement-governed communication among artificial cellular agents and offers insights into the design of functional systems empowered by collective chemical intelligence.

Keywords:  3D printing; DNA nanoscience; cellular communication; reaction-diffusion system; strand displacement reaction

DOI:  https://doi.org/10.1021/acsnano.5c20505
Nat Commun. 2026 03 15. pii: 2492. [Epub ahead of print]17(1):

Synthetic aptamer mechanoreceptors enable cell-specific force sensing and temporal control via DNA circuits.

Tao Xu, Soumya Sethi, Christoph Drees, Andreas Walther.

Cells interpret mechanical cues from their microenvironment with spatiotemporal precision to guide adaptive behaviors. However, engineering synthetic mechanosensing systems with both cell-specificity and programmability remains challenging, especially when targeting ubiquitous classical mechanoreceptors. Here, we introduce an all-DNA mechanosensing platform based on aptamers that transmit force through noncanonical surface receptors. Aptamer-receptor recognition acts as a molecular gate for force transduction, enabling the design of mechanoprobes with cell-type selectivity. These probes interpret diverse mechanical inputs via distinct mechanisms, including actomyosin-driven contractility and membrane ruffling during macropinocytosis. By integrating aptamer mechanoprobes with upstream DNA reaction networks, we achieve reversible and temporally programmable mechanoresponses. This modular, all-nucleic-acid system offers a general framework for constructing tunable mechanotransduction circuits. It expands the design space for synthetic mechanobiology and provides opportunities for autonomous, multi-layered mechanical-biochemical regulation in tissue engineering, morphogenesis, and dynamic cell programming.

DOI: https://doi.org/10.1038/s41467-026-70765-w
Nature. 2026 Mar 18.

Synthetic circuits for cell ratio control.

Bolin An, Tzu-Chieh Tang, Qian Zhang, Teng Wang, Yanyi Wang, Kesheng Gan, Kun Liu, Daniel L Zhang, Yuzhu Liu, Yu Kui Pan, Min Yu, William M Shaw, Qianyi Liang, Yaomin Wang, Christopher A Vaiana, Chunbo Lou, Christopher A Voigt, Timothy K Lu, George M Church, Chao Zhong.

Recent advances in genetic engineering have provided diverse tools for artificially diversifying both prokaryotic and eukaryotic cell populations1-6. However, achieving precise control over the ratios of multiple cell types within a population derived from a single founder remains a major challenge. Here we introduce a suite of recombinase-mediated genetic devices designed to accurately control population ratios, enabling the distribution of distinct functionalities across multiple cell types. We systematically evaluated key parameters that influence recombination efficiency and developed data-driven models to reliably predict binary differentiation outcomes. Using these devices, we constructed parallel and series circuit topologies to implement user-defined, multistep cell-fate branching programs. The branching devices facilitated the autonomous differentiation of precision fermentation consortia from a single founder yeast strain, optimizing cell-type ratios for applications such as pigmentation and cellulose degradation. Similar effects were obtained with mammalian cells. We also engineered multicellular aggregates with genetically encoded morphologies by coordinating self-organization through cell adhesion molecules. Our work provides a comprehensive characterization of recombinase-based cell-fate branching mechanisms and introduces an approach for constructing synthetic consortia and multicellular assemblies.

DOI: https://doi.org/10.1038/s41586-026-10259-3
Bioact Mater. 2026 Aug;62 282-293

Reprogrammable 4D tissue engineering hydrogel scaffold via reversible ion printing.

Aixiang Ding, Fang Tang, Sriramya Ayyagari, Eben Alsberg.

  Shape-morphable hydrogel scaffolds recapitulating morphological dynamism of native tissues represent an elegant tool for tissue engineering (TE) applications. Current morphable hydrogels are predominantly based on multimaterial structures, which involve complicated and time-consuming fabrication protocols, and are often limited to unidirectional deformation. This work reports on the development of a transformable hydrogel system using a fast, simple, and robust fabrication approach for manipulating the shapes of soft tissues at defined maturation states. Simply by using an ion-transfer printing (ITP) technology, a tunable ion crosslinking density gradient across the hydrogel thickness has been incorporated, which enables preprogrammable deformations upon further swelling in cell culture media. Combining with a surface patterning technology, cell-laden constructs (bioconstructs) capable of morphing in multiple directions are deformed into sophisticated configurations. Not only can the deformed bioconstructs recover their original shapes by chemical treatment, but at user-defined times they can also be incorporated with new, different spatially controlled gradient crosslinking via the ITP process, conferring 3D bioconstruct shape reprogrammability. In this manner, unique "3D-to-3D" shape conversions have been realized. Finally, effective shape manipulation in engineered cartilage-like tissue constructs has been demonstrated. These morphable scaffolds may advance 4D TE by enabling sophisticated spatiotemporal control over construct shape evolution.

Keywords:  4D printing; Biomimicry; Crosslinking gradient; Shape morphing; Tissue development

DOI:  https://doi.org/10.1016/j.bioactmat.2026.03.011
Biomater Sci. 2026 Mar 16.

Modular noncovalent functionalization of electrospun piezoelectric scaffolds with bioactive nanocarriers.

Sarah Payne Bortel, Sumayia Saif Jaima Chowdhury, Jeremy Cheng, Daniella Uvaldo, Mackenzie Wright, Anna Marie Kylat, Treena Livingston Arinzeh, Santiago Correa.

Electrospun scaffolds offer a promising platform for immune-instructive materials, but stable and modular functionalization with bioactive signals remains a technical challenge. Here, we develop a surface coating strategy for electrospun scaffolds that consist of poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE), a piezoelectric polymer, using electrostatic adsorption of charged nanoparticles. We show that under certain conditions, these piezoelectric scaffolds are suitable substrates for electrostatic self-assembly, and that the density of nanoparticle coatings can be tuned by adjusting buffer pH, ionic strength, and nanoparticle concentration. This approach enables robust and uniform coating with both polymeric nanoparticles and soft nanocarriers such as liposomes, without requiring covalent surface modification of the scaffold. Liposome-coated scaffolds are cytocompatible with adherent epithelial and suspension immune cells and support lipid exchange at the cell-material interface. Using a supramolecular tethering strategy, we use liposome coatings to present interleukin-15 (IL-15) from the scaffold surface and demonstrate localized, sustained cytokine signaling. Together, these findings establish a modular approach for post-fabrication, noncovalent scaffold functionalization with bioactive nanocarriers, offering new opportunities for tissue and immune engineering.

DOI: https://doi.org/10.1039/d5bm01563d
Sci Adv. 2026 Mar 20. 12(12): eaeb3401

Bioelectronic synthesis of hydrogen sulfide enables spatiotemporal regulation of protein modification and cellular redox.

Lian Lim, Changho Lee, Jaewoong Lee, Myeongeun Lee, Yongha Kim, Tae Kyoung Lee, Gwangbin Lee, Jinsoo Kim, Sang Yeon Oh, Jihan Kim, Jimin Park.

Reactive signaling molecules such as hydrogen sulfide (H2S) regulate protein function and cellular redox balance, yet their instability makes precise delivery in biological systems challenging. Existing bioelectronic platforms primarily target stable molecules and often lack the ability to control transient molecules with spatiotemporal precision. We develop a bioelectronic platform that uses electrochemical reactions to directly generate and deliver H2S from biocompatible thiosulfate precursors near living cells. Through electrocatalyst screening, theoretical modeling, and product analysis, we demonstrate that biocompatible metal cathodes with low metal-hydrogen binding energy catalyze H2S production while suppressing side reactions. Programmable electronic inputs, including electrolysis time and applied voltage, quantitatively control distance- and time-dependent H2S release at the bioelectronic interface while maintaining physiological compatibility. This spatiotemporally modulated H2S synthesis enables on-demand activation of ion channels through protein sulfhydration and restoration of intracellular redox balance under oxidative stress. Our platform broadens the functional scope of bioelectronics and establishes electrosynthesis as a modality for dynamic communication between electronics and biology.

DOI: https://doi.org/10.1126/sciadv.aeb3401
Lab Chip. 2026 Mar 17.

Multiphasic droplet microfluidics platform for controlled bacteria and mammalian cell co-culture.

Ibraheem Alshareedah, Anand Kumar.

Microfluidics has revolutionized high-throughput miniaturized biological assays. However, co-culture of mammalian cells and bacteria remains challenging in microfluidic systems due to incompatible growth requirements, limited spatial control, and the requirement for a mammalian cell adhesion matrix. Here, we present a microfluidic platform that generates multiphasic droplets which encapsulate mammalian and bacterial cells, enabling their direct and indirect co-culture. By combining photopolymerizable hydrogels with polymer phase separation, we generate core-shell droplets composed of a liquid and a hydrogel compartment. The hydrogel compartment supports mammalian cell adhesion and culture, while the liquid compartment sustains bacterial growth. We demonstrate two droplet architectures that allow physical bacteria-mammalian cell contacts or enforce complete physical separation, representing direct and indirect co-culture. Our multiphasic droplets are stable, customizable, able to sustain co-culture for over 24 hours, and compatible with fluorescence-based cell sorting technologies. Overall, our multiphasic droplet microfluidic platform provides a scalable and versatile tool for high-throughput co-culture and screening of host-microbe interactions.

DOI: https://doi.org/10.1039/d6lc00016a
ACS Synth Biol. 2026 Mar 18.

Automated Assembly of Programmable RNA-Based Sensors.

James M Robson, Nery R Arevalos, Alexander A Green.

  Engineered programmable RNA sensors have been applied in low-cost diagnostics, endogenous RNA detection, and multi-input genetic circuits. However, designing, producing, and screening high-performance RNA sensors remains time-consuming and labor intensive. Here, we present an automated plasmid assembly pipeline using liquid handling robotics to enable high-throughput construction of plasmids with arbitrary sequences. We compare automated and manual assembly methods using the NGS Hamilton Microlab STAR across two plasmid backbones to evaluate efficiency and reliability. As a proof of concept, we use this modular platform to construct a diverse set of programmable RNA regulators, including toehold switch riboregulators targeting viral RNAs, single-nucleotide-specific programmable riboregulators for discrimination of SARS-CoV-2 spike gene mutations, and metal-responsive riboswitches. In total, we construct 174 plasmids and test the designed methods by comparing both manual and automated assembly. We further demonstrate that the assembled toehold switch plasmids are functional in both bacterial and cell-free expression systems.

Keywords:  RNA sensors; automation; cell-free system; cloning; diagnostics; riboregulators

DOI:  https://doi.org/10.1021/acssynbio.5c00560
Macromol Rapid Commun. 2026 Mar 15. e00006

Light-Mediated Synthesis of Degradable Polymers With Complex Architectures Using α-Lipoic Acid as a Cleavable Comonomer.

Dongjoo Lee, Hanqing Wang, Xinyuan Zuo, Abdullah Alazmi, Shu-Yan Jiang, Rafael Verduzco.

  The annual global production of polymeric materials is approaching 500 Mt, and the disposal and recycling of these polymers remains a significant challenge due in large part to the persistence of backbone carbon-carbon bonds, which require extreme conditions to degrade. A potential solution is to design polymers that are robust and stable during normal use but can be degraded on demand and enable new strategies for degradation and recycling. Herein, we present a versatile light-mediated synthetic approach to prepare degradable polymers, including both linear and nonlinear architectures. Our approach involves the controlled radical polymerization via reversible addition-fragmentation chain transfer (RAFT) of various vinyl monomers along with 1,2-dithiolane-based comonomers, which introduce disulfide bonds into the polymer backbone, enabling efficient degradation. Similar to conventional photoiniferter RAFT polymerization, light initiates the copolymerization and simultaneously generates thiyl radicals that react with growing chain radicals to propagate the polymerization. We demonstrate through the use of 1,2-dithiolane-functionalized inimers and selective excitation of CTAs that we can produce nonlinear polymers, including hyperbranched and graft polymers. This mild and versatile approach offers a promising strategy for designing and synthesizing degradable polymers with tailored architectures.

Keywords:  degradable polymers; dithiol polymers; lipoic acid; photopolymerization; sustainability

DOI:  https://doi.org/10.1002/marc.202600006
Mol Syst Biol. 2026 Mar 16.

A universal surface functionalization technique to chemically enhance live microbial cells.

Gabriel T Vercelli, Xingcheng Zhou, Stefany Moreno-Gámez, Rashi R Jeeda, Rachel Gregor, Jonasz Słomka, Akorfa Dagadu, Ariel L Furst, Otto X Cordero.

  Microbial surface functionalization is a powerful strategy for endowing microbes with novel, non-genetic functions. However, existing methods are often species-specific, limited in scope, and compromise cell viability. Here, we present a universal and modular platform for high-density, reproducible surface functionalization across diverse microbial species-including Gram-positive, Gram-negative, aerobic, and anaerobic bacteria-using multiple molecular classes such as fluorophores, enzymes, and nucleic acids. Our method preserves cell viability and achieves 50× higher functionalization efficiency than previous methods with a standardized protocol applicable to any azide-containing molecule. Applications of the method show reproducible and tunable phenotypic outcomes at the single-cell level: fluorophore labeling yielded adjustable fluorescence, β-lactamase conferred scalable antibiotic resistance, and DNA coatings modulated adhesion and aggregation. This platform provides quantitative, non-genetic control over microbial phenotypes and complements genetic engineering approaches. It enables new possibilities for microbial design in biotechnology, medicine, and environmental applications where genetic modification is impractical or undesirable.

Keywords:  Cell Surface Functionalization; Click Chemistry; Microbial Aggregates; Molecular Engineering; Non-genetic Engineering

DOI:  https://doi.org/10.1038/s44320-026-00202-z
Small. 2026 Mar 20. e12642

Orthogonal Tri-Modular Coiled-Coil Assembly for Programmable Multi-Cargo Display on Escherichia coli Nissle 1917.

Yong Joon Cho, Gyu-Jin Lee, Jong-Ha Park, Sung In Lim.

  Live biotherapeutic products (LBPs) represent emerging living medicines capable of site-specific intervention; however, current strategies for surface functionalization rely predominantly on static genetic fusion or covalent modification, limiting multiplexing and dynamic reconfiguration. Here, we engineer TriSCs (Tri-specific Scaffold Cells), a tri-modular and orthogonally programmable living scaffold based on Escherichia coli Nissle 1917. Three distinct α-helical motifs are displayed on the bacterial outer membrane, forming a reconfigurable biointerface that enables spontaneous, highly specific, and reversible payload assembly via coiled-coil interactions. This mix-and-go strategy allows simultaneous and selective recruitment of multiple functional modules without structural interference. Spatial co-display of a DR5 agonistic nanobody and an EGFR-targeting nanobody produces enhanced anticancer activity compared to soluble combinations, underscoring the impact of surface-organized signaling. In parallel, modular incorporation of a fluorescent reporter enables real-time bioimaging. By integrating orthogonality, reversibility, and multiplex capability within a single living chassis, TriSCs establish a dynamic and programmable LBP platform for precision theranostics and next-generation bioengineered therapeutics.

Keywords:  coiled‐coil interactions; live biotherapeutic products; multiplex surface display; orthogonal assembly; programmable living scaffold

DOI:  https://doi.org/10.1002/smll.202512642
Biochemistry. 2026 Mar 17.

Design Strategies for Advanced Biomaterials Functionalized with Bioactive Peptides.

Stella M Trickett, Tania L López-Silva.

  A vast library of bioactive peptides provides a versatile toolkit for engineering biological functionality into materials. This peptide repertoire encompasses a broad range of bioactivities, including cell adhesion, protease lability, signaling activation, and immunomodulation. As a result, these peptides have been widely used in biomaterial design to instruct cell behavior and control biological outcomes. Given the complexity and highly dynamic nature of native cellular microenvironments, emerging approaches focus on developing multifunctional and stimuli-responsive biomaterials that better recapitulate these biological systems. Designing such materials requires integrating biochemical mechanisms that drive specific cellular responses while optimizing material properties to enhance desired functionality. In this review, we describe emerging design strategies and key considerations for peptide-functionalized materials, with an emphasis on the molecular interactions and biochemical mechanisms that inform their design. We discuss how synergistic cues, peptide structural conformation, and modes of motif presentation are used to regulate cell-material interactions and downstream signaling. We also highlight molecular- and material-based strategies to impart endogenous and exogenous stimulus-responsive behavior, as well as the influence of intrinsic material properties on peptide bioactivity. Advances in computational and data-driven approaches for the discovery and optimization of de novo bioactive peptides and biomaterials, coupled with new insights into biological mechanisms and protein structures, are accelerating the design of materials that more closely recapitulate natural environments for diverse biomedical applications.

Keywords:  bioactive peptides; biomaterials; cell-materials interactions; multifunctional materials; stimulus-responsive materials

DOI:  https://doi.org/10.1021/acs.biochem.6c00018
Proc Natl Acad Sci U S A. 2026 Mar 24. 123(12): e2527410123

A DNA-encoded recipe to direct multistage colloidal assembly.

Pepijn G Moerman, Cheng-Hung Chou, Thomas E Videbæk, W Benjamin Rogers, Rebecca Schulman.

  In equilibrium self-assembly, microscopic building blocks spontaneously self-organize into stable structures as dictated by their interaction potentials, which limits the accessible structural features to those that correspond to global minima in free energy landscapes; they are often ordered and periodic on length scales comparable to the building block size. Coupling the assembly process to an exergonic reaction drives the system out of equilibrium so that an assembly pathway can be engineered to target a specific kinetically stabilized state, which in principle opens up a vast design space with access to diverse complex structures with features on multiple length scales. However, the question of how such features might be specifically targeted remains unanswered. Here, we explore this design space using a DNA-encoded recipe consisting of multiple biomolecular reactions that dictate the time-dependent binding strength and specificity of each type of subunit in the sample independently, which makes it possible to program an assembly pathway that leads to a kinetically trapped final state. With this kinetic control, we show that the same set of building blocks can form clusters with different final structures. These structures, with tunable core-shell compositions, have feature sizes much larger than the building block size and are governed by the DNA-encoded assembly kinetics. Tuning the timing of individual biomolecular reactions using DNA-encoded recipes offers the opportunity to independently regulate how the many interactions of a large set of coassembling components evolve over time, opening up the potential of creating morphogenesis-like assembly processes involving engineered species.

Keywords:  DNA-coated colloids; assembly kinetics; nonequilibrium

DOI:  https://doi.org/10.1073/pnas.2527410123
Biomacromolecules. 2026 Mar 20.

Thermoresponsive Gels Based on Cross-Linked Polymer-Grafted Cellulose Nanocrystals.

Matilde Folkesson, Justus Paul Wesseler, Carolina Pierucci, Chris Rader, Christoph Weder, Alessandro Ianiro, José Augusto Berrocal.

Stimuli-responsive nanocomposite hydrogels have garnered significant interest as alternatives to conventional hydrogels, enabling the engineering of stimuli-responsive behavior and network connectivity through composition and architecture. Here, we report thermoresponsive, "one-component" nanocomposite hydrogels composed of copolymer-grafted cellulose nanocrystals (CNCs). Thermoresponsive polyacrylamides or poly(oligoethylene glycol acrylate) copolymers bearing terminal olefin side chains were grafted from the CNC surfaces using atom-transfer radical polymerization, yielding densely grafted hairy nanoparticles (HNPs). The HNPs were cross-linked via UV-mediated thiol-ene click chemistry to form hydrogels. The resulting networks exhibit reversible LCST-type swelling and deswelling, with thermoresponsive and mechanical behavior governed by graft chemistry, architecture, and solvation. Comparative experiments using CNC-free and physically mixed hydrogels show that, at the low CNC loadings employed here, mechanical properties are shaped predominantly by chain entanglement and solvation, rather than by reinforcement from the nanocrystals.

DOI: https://doi.org/10.1021/acs.biomac.5c02262
Proc Natl Acad Sci U S A. 2026 Mar 24. 123(12): e2531136123

Transiently amplified fluctuations assemble dissipative materials.

Tae Hyun Ueon, Joseph P Patterson, Jason R Green.

  Chemical reactions assemble supramolecular materials with finite lifetimes, responsiveness to stimuli, and the capacity to self-heal after perturbation. These dynamic behaviors arise from a reaction cycle that switches a molecule between associating and nonassociating states via two independent pathways, each driven by a distinct chemical reagent. Here, we show that this same network architecture can transiently amplify small concentration fluctuations, leading to a pronounced, spontaneous increase in the yield of assembled material. Following a small perturbation in reagent supply, the chemical kinetics do not immediately relax toward a steady state; instead, they initially evolve farther from equilibrium and promote the assembly of thermodynamically unstable products. For a model supramolecular system, this dynamical effect produces a strong transient amplification of assembled material above its steady-state level. By analyzing the conditions for transient growth and its maximum, we find that steady states farther from detailed balance can exhibit stronger amplification and higher transient yields. Although these excursions are short-lived, accumulating experimental evidence suggests that analogous dynamics already occur in chemically active supramolecular materials. The mathematically precise conditions identified here suggest opportunities to amplify fluctuations in the design of responsive materials.

Keywords:  dissipative self-assembly; nonnormality; supramolecular materials; transient growth

DOI:  https://doi.org/10.1073/pnas.2531136123
J Am Chem Soc. 2026 Mar 18.

Light-Driven C4 Biosynthesis from CO2 and H2O via Engineered Photocatalyst-Microbial Consortia.

Haiyi Xu, Jicong Zhang, Ke Shi, Jiaming Zhang, Boyang Zhang, Mingming Guo, Xueli Zhang, Ke Li, Guijun Ma, Xiang Gao, Xinyu Wang, Chao Zhong.

The development of sustainable technologies for converting CO2 into value-added chemicals using solar energy remains a critical challenge. We presented a biohybrid system integrating Z-scheme photocatalysts with engineered microbial consortia for light-driven succinic acid production from CO2 and H2O without sacrificial agents. The system combined Escherichia coli biofilms expressing formate dehydrogenase for photoelectrochemical CO2 reduction to formate with adaptively evolved Vibrio natriegens for formate upgrading to succinic acid. This configuration achieved 0.06 mM succinic acid in 6 h with an apparent quantum yield of 0.154%. The biofilms maintained conformal contact with photocatalysts through four operational cycles, while V. natriegens viability increased by 11% owing to the formate provided by the biohybrid sheet. Further, isotopic tracing revealed approximately 20% carbon incorporation from CO2. This work establishes a sustainable platform for solar-driven multicarbon synthesis through rational integration of photocatalysis and synthetic microbial consortia.

DOI: https://doi.org/10.1021/jacs.5c16572
Biomater Adv. 2026 Mar 17. pii: S2772-9508(26)00126-3. [Epub ahead of print]184 214828

Engineering ECM-mimetic scaffolds from biological macromolecules for physiologically relevant tumoroid models.

Priya Bhatt, Prajnadipti Sahu, Pragyan Mohapatra, Manu Smriti Singh, Aniruddha Roy.

  The tumor extracellular matrix (ECM) is a dynamic, tissue-specific network of structural proteins, adhesive glycoproteins, and glycosaminoglycans that governs cancer cell behaviour, mechanotransduction, invasion, and therapeutic response. While conventional 2D models fail to reproduce these cues, cell-based 3D tumoroids, mainly derived from cancer cell lines or patient biopsies, have advanced preclinical modelling by restoring aspects of tumor heterogeneity and biochemical gradients. However, their stability, architecture, and predictive value remain limited in the absence of ECM-mimetic scaffolds. This review synthesizes current knowledge on tumor ECM macromolecules as modular design elements, detailing how their biochemical interactions and mechanical roles can be leveraged to engineer physiologically relevant scaffolds. We evaluate major classes of ECM-mimetic platforms, including decellularized matrices, biological macromolecule-based hydrogels, synthetic and hybrid polymer networks, and commercially available systems. We examine fabrication strategies that enable tunable control over stiffness, architecture, and degradation. A materials-centered analytical framework is presented to link scaffold composition, porosity, viscoelasticity, swelling behaviour, and degradability to key tumor phenotypes, including EMT, hypoxia gradients, and drug response. By integrating stiffness landscapes from diverse tissues, we propose tumor-type-specific design maps to guide rational material selection for various cancers. We conclude by outlining the critical materials challenges that must be addressed to advance translational 3D tumor models, including the development of chemically defined scaffolds, integration with microfluidic platforms, high-throughput fabrication, and standardization for reproducible clinical application. Together, these insights position ECM-mimetic biomaterials not merely as culture supports but as engineered microenvironments essential for next-generation mechanistic studies and precision oncology.

Keywords:  3D-tumoroid; Biophysical characterization; Bioprinting; Extracellular matrix; Scaffold

DOI:  https://doi.org/10.1016/j.bioadv.2026.214828
Macromolecules. 2026 Mar 10. 59(5): 2767-2779

Dual-Pathway Strategy for Click-Type Functionalization and Programmable Polymer Deconstruction.

Ivan O Levkovsky, Lucca Trachsel, Hironobu Murata, Krzysztof Matyjaszewski.

Developing polymeric materials that combine precise, modular functionalization with programmed backbone degradability remains an outstanding challenge in macromolecular engineering. Herein, we present a molecular design strategy that integrates orthogonal postpolymerization modification with selective, stimulus-responsive backbone degradability within a single macromolecular platform. The ring-opening polymerization of 1,2-dithiolanes introduces cleavable disulfide linkages into polymer backbones, providing a powerful route to degradable materials under biologically relevant reducing conditions. By incorporating a β-triketone (TK) moiety into an α-lipoic-acid-derived 1,2-dithiolane, we synthesized triketone-lipoic acid (TKLA), a dual-functional monomer that combines click-type, catalyst-free amine ligation with programmed backbone degradability. Leveraging photoinduced electron/energy-transfer reversible addition-fragmentation chain-transfer (PET-RAFT) copolymerization of TKLA with acrylate and acrylamide monomers, we accessed well-defined copolymers containing both pendant TK groups and disulfide-rich backbones in a single synthetic step. Under mild conditions, TK-bearing copolymers react quantitatively with a broad scope of amines to form β,β'-diketoenamines (DKEs), enabling modular installation of hydrophilic, hydrophobic, charged, and bioactive substituents. Importantly, these DKE moieties are not static but participate in associative transamination, allowing dynamic exchange and reconfiguration of installed functionalities. Meanwhile, the disulfide-containing backbones fragment cleanly and selectively under reducing environments, affording controlled deconstruction while preserving, or transforming, the appended side-chain chemistry. Overall, the integration of efficient, chemoselective β-triketone-amine condensation with LA-based degradability within a single monomer framework establishes a molecular design strategy for constructing functional, recyclable, and stimuli-responsive polymer architectures.

DOI: https://doi.org/10.1021/acs.macromol.6c00380
Proc Natl Acad Sci U S A. 2026 Mar 24. 123(12): e2536311123

Nonmonotonic rate-dependent adhesion of hydrogels.

Dongjing He, Jiahe Huang, Yuhang Hu.

  Hydrogel adhesion underlies a wide range of biological and engineering functions, yet its rate dependence remains poorly understood. Classical adhesive systems exhibit a monotonic increase in adhesion strength with separation rate, a behavior attributed to bond stress relaxation. Here, we show that hydrogels fundamentally deviate from this paradigm. Using atomic force microscopy-based indentation over six orders of magnitude in retraction rate, we find that the pull-off force first decreases and then increases, revealing a distinctly nonmonotonic rate dependence in hydrogels. To explain this behavior, we develop a quantitative model that couples the deformation of the hydrogel with a rate-dependent traction carried by interfacial bonds with distinct association and dissociation kinetics. The model reproduces the full pull-off force spectrum exhibiting the nonmonotonic behavior and predicts the evolution of the contact radius during detachment. In situ confocal microscopy measurements of contact-area dynamics confirm these predictions, providing independent validation of the kinetic mechanism. Together, the experiments and theory reveal that hydrogel adhesion is governed by a competition between time-dependent bond formation, which strengthens adhesion at slow rates, and limited bond relaxation, which enhances traction at fast rates. This interplay produces a broad intermediate regime in which reduced contact time suppresses bond buildup and weakens adhesion. Our findings identify a previously unrecognized adhesion regime in polymeric materials and provide a unified framework for understanding and designing hydrogel interfaces whose performance depends sensitively on rate, contact history, and interfacial bonding kinetics.

Keywords:  dynamic bonding; hydrogel; rate-dependent adhesion

DOI:  https://doi.org/10.1073/pnas.2536311123
Mater Horiz. 2026 Mar 20.

Mixed ionic-electronic conducting eutectic soft materials for bioelectronics.

Mahboubeh Firuzeh, Estefano Giuzio, Aitor Larrañaga, Matias L Picchio.

Bioelectronic devices represent a rapidly expanding frontier at the interface of materials science, biology, and electronics, with the potential to transform healthcare by enabling seamless communication between living tissues and engineered systems. A central challenge in this field is the design of soft materials that can efficiently transport both ionic and electronic charge carriers, thereby bridging the fundamental mismatch between biological and electronic signal transduction. In this opinion, we argue that eutectic systems offer a powerful yet underexplored platform for engineering mixed ionic-electronic conducting soft materials. Eutectic mixtures, by virtue of their unique phase behavior, tunable molecular interactions, and inherent structural flexibility, provide an exceptional starting point for tailoring materials that combine biocompatibility, adaptability, and functional conductivity. We highlight how eutectic design principles can be leveraged to expand the palette of soft conductors, offering pathways to address persistent challenges such as stability, processability, and integration with complex biological environments. Looking forward, we outline key research directions to unlock the full potential of eutectic-derived conductors in advancing next-generation bioelectronic systems.

DOI: https://doi.org/10.1039/d5mh02312b
Metab Eng. 2026 Mar 16. pii: S1096-7176(26)00043-1. [Epub ahead of print]96 104-112

Orthogonal quorum sensing circuits enable dynamic regulation in Escherichia coli.

Michael J Ream, Kristala L J Prather.

  Engineers have effectively employed quorum sensing (QS) in a variety of applications to dynamically regulate gene expression. Particular emphasis has been placed on the class of well-studied systems that use acyl homoserine lactones (AHL) as signaling molecules due to their ease of implementation, high expression level, and previous optimization efforts. However, many of these AHL systems respond to ligands with similar structures, causing crosstalk when combined in multi-layered regulation strategies. Here, we first confirmed the functional orthogonality of the previously identified Tra and Rpa quorum sensing circuits within a single strain of Escherichia coli MG1655 by analyzing the pairwise interactions of several AHL systems. The orthogonality of the systems allowed for independent tuning of two control strategies, which was then applied to the naringenin biosynthetic pathway. The Tra system was used to activate expression of tyrosine-ammonia lyase (TAL) and 4-coumaroyl-CoA ligase (4CL), controlling the expression of the upstream pathway. Meanwhile, Rpa dynamically downregulated competing pathways of native metabolism via CRISPRi to increase availability of malonyl-CoA. This multi-layered approach provided finely-tuned metabolic control that allowed for a combinatorial screening of optimal dynamic regulation. A strain library with varying promoter strengths was then built to test AHL induction timings and screened for target compound production. Naringenin production from this autoinducible method reached a final titer of 71.02 ± 3.96 mg/L in flask-scale fermentation.

Keywords:  CRISPRi; Dynamic regulation; Quorum sensing; Synthetic biology

DOI:  https://doi.org/10.1016/j.ymben.2026.03.009
Sci Adv. 2026 Mar 20. 12(12): eaec3182

Magnetic coupling transforms random snapping into ordered sequences in soft metamaterials.

Haoze Sun, Gabriel Alkuino, Yinding Chi, Yevhen Zabila, Haitao Qing, Denys Makarov, Teng Zhang, Jie Yin.

Mechanical metamaterials achieve multistep, programmable responses through sequential deformation driven by snapping instabilities, yet these sequences are typically governed by unavoidable imperfections, resulting in random and uncontrollable behavior. Here, we harness intra- and interlayer magnetic interactions coupled with elasticity to reprogram the ordering of sequential buckling instabilities in kirigami-inspired soft magnetic metamaterials. In single-layer systems, intralayer coupling among magnetized units produces random snapping sequences but generates strongly nonlinear-spiked force-displacement responses with pronounced hysteresis, in contrast to the simultaneous buckling of unmagnetized sheets. In multilayer assemblies, interlayer magnetic interactions trigger chain reaction-like propagation, transforming randomness into robust, directional snapping across structures. This mechanism establishes a paradigm for deterministic, multistep mechanical responses without continuously applied fields and opens avenues for adaptive materials in energy dissipation, waveguiding, reconfigurable soft robotics, and biomedical devices.

DOI: https://doi.org/10.1126/sciadv.aec3182
ACS Appl Mater Interfaces. 2026 Mar 20.

Precise and Parallel Fabrication of Microactuator Arrays via Interfacial Supramolecular Adhesion.

Siyuan Liu, Bingkun Zhao, Kuai Yu, Yongsheng Wu, Guangyuan Wang, Qian Zhang, Guangtao Zhao, Feng Shi, Mengjiao Cheng.

  Scalable manufacturing of microactuators with heterogeneous materials, such as bilayer hydrogels, remains a challenge for soft robotics in collective intelligence and micromanipulation. Current methods, like manual assembly and three-dimensional (3D) printing, limit scalability and result in bulky devices with slow actuation. We present a precise, parallel strategy─macroscopic supramolecular assembly (MSA)─that enables large-scale production of microactuators with rapid response. Using the widely studied thermos-responsive poly(N-isopropylacrylamide) (PNIPAM)/polyacrylamide (PAAm) system, we apply the noncovalent interfacial links between β-cyclodextrin (CD) and adamantane (Ad) groups to fabricate PNIPAM/PAAm microactuators. PNIPAM-CD microhydrogel arrays on a donor substrate are "picked" and "placed" onto PAAm-Ad microhydrogels using a mask aligner to control the precision. In-situ measurements of interfacial forces confirm that MSA kinetics favor adhesion control and dynamic binding/debonding modeling reveals the interfacial interactive mechanism. The microactuators show an ultrafast response (0.25 s) and complete deformation in 1.17 s─almost 2 orders of magnitude faster than macroscopic counterparts─due to enhanced mass and heat transfer at the microscale. This strategy provides a scalable route for parallel fabrication of miniaturized devices with rapid, reliable actuation.

Keywords:  interfacial molecular recognition; macroscopic supramolecular assembly; miniaturization; parallel fabrication; pick and place

DOI:  https://doi.org/10.1021/acsami.6c02764
Adv Sci (Weinh). 2026 Mar 17. e11302

Cellular Snowballing: Cell Adhesion and Migration Drive the Self-Assembly of Cell-Microgel Biohybrid Spheroids.

Zaman Ataie, Sina Kheirabadi, Changhao Li, Aneesh Risbud, Aswathy Sebastian, Istvan Albert, Sulin Zhang, Amir Sheikhi.

  Creating three-dimensional (3D) tissue models using cell spheroids that recapitulate the complicated structures and functions of human tissues is essential for advancing new approach methodologies used in drug testing/screening, disease modeling, and regenerative medicine. However, cell spheroids often have dense cellular structures and subsequently poor cell survival, primarily due to impaired oxygen and metabolite transport. To overcome these limitations, we develop biohybrid spheroids (BHS), self-assembled living-synthetic hybrid aggregates, using adherent cells as assembly engines and hydrogel microparticles (microgels) as extracellular matrix-mimetic substrates. We show the revolving assembly of 3D BHS, driven by progressive cell migration and adhesion via culturing adherent mammalian cells and gelatin methacryloyl microgels, reminiscing a snowballing effect. The aggregation kinetics and terminal size of BHS are tailored by adjusting microgel size and cell-to-microgel ratio. Notably, microgels significantly larger than the cells yield porous, millimeter-sized BHS, facilitating molecular diffusion and improving cell viability. Furthermore, transcriptional analyses show shifts in adhesion, angiogenesis, hypoxia, and proliferation programs in BHS compared with cell spheroids. An agent-based model is developed to recapitulate the snowballing assembly in a geometrically unconstrained environment, providing fundamental insights into the assembly kinetics and the ultimate BHS size and pore features. BHS may open new opportunities for developing predictive and scalable technologies to self-assemble large-scale physiologically relevant tissue models in vitro, potentially transforming the biofabrication of microphysiological systems.

Keywords:  granular hydrogel; living material; microgel; new approach methodologies; spheroid; tissue engineering

DOI:  https://doi.org/10.1002/advs.202511302
Nat Commun. 2026 03 19. pii: 2620. [Epub ahead of print]17(1):

Engineering synthetic cells with intramembrane domains possessing distinct bilayer asymmetries.

Naresh Yandrapalli, Tina Seemann, Reinhard Lipowsky, Tom Robinson.

Our understanding of how membrane asymmetry governs biological function is limited by the lack of techniques to produce model membranes which can reliably and accurately mimic cellular membrane asymmetry. Not only in terms of asymmetric lipid distribution, but also how that asymmetry can be confined to specific lateral locations across the membrane. Here we present an inverted emulsion method that can be used to produce synthetic cells with symmetric and asymmetric bilayers, as well as phase separation where the intermembrane domains possess distinct bilayer asymmetries. We assess the degree of lipid asymmetry using protein-lipid interaction and quenching assays. Surprisingly, the synthetic cells with asymmetric and phase separated membranes displayed pronounced curvature of the domains and resulted in membrane budding and division. Overall, this work develops biomimetic membranes with lipid compositions akin to natural biomembranes - an essential element in the development of functional synthetic cells.

DOI: https://doi.org/10.1038/s41467-026-68997-x
Nat Commun. 2026 Mar 19.

Volumetric 3D printing of a fluoropolymer and closed-loop chemical recycling of its fluorinated content.

Quinten Thijssen, Antonio Jaen-Ortega, Nele Pien, Sandra Van Vlierberghe.

Fluorinated polymers are indispensable in fields such as microfluidics, electronics, and biomedical engineering. Yet, their chemical stability leads to long-term environmental persistence, rendering end-of-life management essential. In parallel, their insolubility and lack of melt behavior complicate fabrication into complex geometries, restricting their use in 3D printing. Here, a fluorinated photoresist is introduced that enables tomographic volumetric 3D printing with closed-loop chemical recycling of its fluorinated content. The photoresist-based on an alkene-functionalized fluorinated diol and a multifunctional thiol-supports rapid fabrication of centimeter-scale objects with reproducible feature sizes down to 56μm, among the smallest reported to date. Selective urethane hydrolysis under alkaline conditions yields ~97% recovery of the fluorinated monomer. The recovered monomer is re-functionalized and reprinted without loss of print fidelity, thermal stability, or mechanical performance. Volumetric 3D printed parts are biocompatible in vitro, supporting potential biomedical use. This represents the first demonstration of high-resolution tomographic volumetric printing of a fluoropolymer with closed-loop chemical recycling of its fluorinated content.

DOI: https://doi.org/10.1038/s41467-026-70897-z
ACS Appl Mater Interfaces. 2026 Mar 17.

Manufacturing Silk Fibroin Hollow Nanoyarns as Fundamental Units for Advanced Medical Textiles.

Athanasios Papakonstantinou, Maria Gabriella Fois, Sergio Acosta, Stephan Rütten, Alexander Kopp, Stefan Jockenhoevel, Alicia Fernández-Colino.

  Nature-inspired designs aim to replicate the hierarchical structure observed in native tissues. Fibers serve as fundamental modular units, enabling the fabrication of complex architectures for the engineering of medical textiles and tissue equivalents. However, synthetic yarns lack inherent biological cues to support tissue integration, leading to a growing interest in yarns derived from natural materials. Here, we describe for the first time the fabrication of hollow nanoyarns from pure silk fibroin (SF) using an advanced funnel electrospinning process. This yielded long SF nanoyarns, spanning several meters, with adequate tensile strength (1.47 MPa) and stretching performance (166.4%). Moreover, the yarns were compatible with autoclaving, permitting effective sterilization and long-term storage, making them suitable for biomedical applications. Indirect cytocompatibility assessment of the scaffolds in accordance with ISO 10993-5 guidelines revealed high metabolic activity for human umbilical vein endothelial cells and human smooth muscle cells, confirming that the scaffolds were nontoxic. Analysis of TNF-α secretion by macrophages showed that the SF scaffolds exhibited low immunogenicity. Furthermore, the structural resilience and flexibility of the yarns supported bottom-up assembly into textile constructs by weaving. This study not only shows for the first time the feasibility of producing SF nanoyarns but also highlights their compelling potential in the field of sustainable and medical textiles.

Keywords:  electrospinning; macrophages; nanoyarn; silk fibroin; textile; tissue engineering

DOI:  https://doi.org/10.1021/acsami.5c23471
Nat Mater. 2026 Mar 17.

Crosslinked ionizable lipids reprogram dendritic cell metabolism for potent mRNA vaccination.

Dongyoon Kim, Ningqiang Gong, Mohamad-Gabriel Alameh, Emily L Han, Hanxun Wang, Jinjin Wang, Ellie Feng, Il-Chul Yoon, Amanda M Murray, Qiangqiang Shi, So-Jeong Moon, Kaitlin Mrksich, Drew Weissman, Michael J Mitchell.

Modulating metabolism in immune cells is an effective approach to induce desired immune responses. Here we develop a lipid nanoparticle (LNP) capable of metabolic reprogramming of dendritic cells for mRNA vaccine applications. Using imidoester-based conjugation chemistry, we design a crosslinked ionizable lipid, C12-2aN, which possesses intrinsic metabolic modulatory properties. This multifunctional ionizable lipid not only promotes effective mRNA expression by facilitating endosomal escape but also stimulates glycolysis through mTORC2 pathway activation. As both an mRNA carrier and a metabolic modulator, C12-2aN LNPs lead to potent vaccine efficacy in both SARS-CoV-2 and OVA cancer vaccine models, resulting in stronger neutralization of pseudovirus infection and improved survival rates, respectively, compared with control LNPs without the crosslinker. Moreover, C12-2aN LNPs outperformed FDA-approved LNPs in terms of reduced off-target delivery and lower immunogenicity. Overall, the integration of mRNA delivery and metabolic reprogramming induced by the ionizable lipid component presents significant potential for next-generation mRNA LNP vaccines.

DOI: https://doi.org/10.1038/s41563-026-02512-x
Sci Adv. 2026 Mar 20. 12(12): eadz9623

Protein overabundance is driven by growth robustness.

H James Choi, Teresa W Lo, Kevin J Cutler, Dean Huang, William Ryan Will, Paul A Wiggins.

Protein expression levels optimize cell fitness: Too low an expression level of essential proteins will slow growth by compromising essential processes, whereas overexpression slows growth by increasing the metabolic load. This trade-off naïvely predicts that cells maximize their fitness by sufficiency, expressing just enough of each essential protein for function. We test this prediction in the naturally competent bacterium Acinetobacter baylyi by characterizing the proliferation dynamics of essential-gene knockouts at a single-cell scale (by imaging) as well as at a genome-wide scale. In these experiments, cells proliferate for multiple generations as target protein levels are diluted from their endogenous levels. This approach facilitates a proteome-scale analysis of the fitness landscape with respect to protein abundance. We find that most essential proteins are subject to a threshold-like fitness landscape: Growth is independent of protein abundance above a critical threshold and arrests below that threshold. We have recently analyzed the implications of this landscape for growth robustness. Confirming signature predictions of this model, we find that (i) roughly 70% of essential proteins are overabundant, (ii) overabundance increases as the expression level decreases, and (iii) the lowest abundance proteins are in vast excess (>10×) of what is required for growth in the typical cell. These results reveal that robustness plays a fundamental role in determining the expression levels of essential genes and that overabundance is a key mechanism for ensuring robust growth.

DOI: https://doi.org/10.1126/sciadv.adz9623
ACS Synth Biol. 2026 Mar 18.

Autonomous Synthesis and Scrambling of Phospholipids, Linked to Recycling of Cofactors in Synthetic Cells.

Jelmer Coenradij, Eleonora Bailoni, Marco Lupacchini, Wessel F Groenhof, Mart Venekamp, Dirk J Slotboom, Arnold J M Driessen, Marten Exterkate, Bert Poolman.

  Compartmentalization of reactions is essential for life and allows nonequilibrium conditions to be maintained within cells. For cell growth, the membranes need to expand through lipid synthesis and a continuous supply of ATP and building blocks. Here, we build a minimal system in vesicles that integrates ATP supply, CTP and CMP recycling, and glycerol-3-phosphate synthesis with the conversion of phosphatidic acid to phosphatidylglycerol. We use four transmembrane proteins and three soluble enzymes to enable autonomous phospholipid synthesis in both the outer and inner leaflets of the membrane. The system displays biphasic lipid synthesis kinetics: a rapid phase with phosphatidylglycerol production in the cis leaflet of the membrane and a slower phase dependent on lipid scrambling. We present previously unreported scramblase activity of two integral membrane proteins: phosphatidylglycerophosphatase A and the mitochondrial ATP/ADP carrier. This work lays the foundation for autonomous lipid biosynthesis in synthetic cells and enables the exploration of emergent properties in compartmentalized systems.

Keywords:  bottom-up synthetic biology; lipid scrambling; lipid synthesis; lipid translocation; membrane reconstitution; recycling of cofactors

DOI:  https://doi.org/10.1021/acssynbio.5c00973
bioRxiv. 2026 Mar 05. pii: 2026.03.03.709093. [Epub ahead of print]

Microembossing Hydrogel Meso-Circuits for Patterning Dissociated Neurons Promotes Ensemble Formation.

Mckennah Thompson, Connor L Beck, Anja Kunze.

Functional networks of wired neurons comprise the basis for neuronal computation and processing. Within neuronal networks, activation of unique ensembles is an important identity of neuronal processing. However, dissociated neuronal networks form homogeneous functional structures with minimal variety in ensemble dynamics. To reintroduce such dynamics, we propose structuring the networks to follow multi-connectivity (micro- and meso-network) paradigms. Here, we use agarose microembossing to physically pattern dissociated neuronal networks across these scales. To perform agarose microembossing, we impress features with poly-dimethyl-siloxane (PDMS) stamps into liquid agarose to emboss features which hold under cold gelation. We validate the viability of primary neurons within the hydrogel patterns and interrogate circuit dynamics through calcium imaging. Patterned features presented with robust ensemble dynamics that are dependent on connectivity paradigms. Altogether, this work establishes a platform for investigating how engaging multi-scale features in the physical network informs neuronal ensemble dynamics.
Clinical Relevance: This work enables further dissociated studies to probe dynamics. We expect that this platform would be especially useful in early-stage drug development or personalized medicine pipelines that need to investigate circuit dynamics.

DOI: https://doi.org/10.64898/2026.03.03.709093
Soft Matter. 2026 Mar 19.

Establishing direct relationships between soft material perception and rheology.

Eric M Burgeson, Jeffrey D Martin, Matjaž Jogan, Simon A Rogers.

In soft materials, a clear relationship between material properties and human sensory perception has long been desired for design of consumer products, but the link has remained evasive. Favorable perception indicates that customers enjoy a product and are likely to continue using it or purchase it again. Perception is frequently measured subjectively by consumer test panels in terms of descriptive sensory words such as softness, smoothness, thickness, etc. that lack established scientific definitions. In this work, we move beyond ambiguous definitions and detail a method to objectively measure and quantify human-material interactions using a representative series of viscoelastic putties. We show that human behaviors have direct rheological meaning with features that are characterized using transient recovery rheology. The rheology scales logarithmically at perception-relevant timescales, akin to Fechner's law. Our work explains variability in user-reported perception and demonstrates a way to construct direct relationships between user behavior and measurable rheology.

DOI: https://doi.org/10.1039/d5sm01286d
RSC Chem Biol. 2026 Mar 03.

Photoclickable Halotag ligands for spatiotemporal multiplexed protein labeling on living cells.

Franziska Walterspiel, Begoña Ugarte-Uribe, Stefan Terjung, Alex Cabrera, Arif Ul Maula Khan, Claire Deo.

Precise spatiotemporal control over fluorescence labeling is a powerful approach for selective marking and tracking of proteins of interest within living systems. Here, we report a photoclickable labeling platform based on the 2,3-diaryl-indanone epoxide (DIO) photoswitch scaffold and the self-labeling protein HaloTag. Upon illumination, the protein-bound DIO undergoes reversible photoisomerization to form a metastable oxidopyrylium ylide (PY) that reacts with ring-strained dipolarophiles via [5 + 2] cycloaddition, enabling covalent spatiotemporal labeling. We synthesize and characterize a library of DIO-HaloTag and DIO-SNAP-tag ligands, systematically examining the effects of linker architecture and scaffold substitution on the photoswitching and photoclick reactivity in vitro and on living cells. We identify a naphthyl-substituted DIO ligand exhibiting superior photoswitching and photoclick efficiency, allowing fast, selective labeling of HaloTagged proteins on the surface of living cells using visible light activation (405 nm). Using this system, we achieve two- and three-color labeling of defined cell surface regions with excellent spatial and temporal precision, additionally allowing combinatorial labeling. Together, this work establishes a versatile framework for multiplexed, light-directed protein labeling compatible with living systems, with promising future applications including multiplexed long-term tracking and cellular barcoding.

DOI: https://doi.org/10.1039/d6cb00017g
Small. 2026 Mar 19. e73110

Chemical Functionalization of 2D Materials.

Xiaoyan Zhang, Nikos Tagmatarchis, Zhong-Shuai Wu, Nazario Martín.

DOI: https://doi.org/10.1002/smll.73110
Proc Natl Acad Sci U S A. 2026 Mar 24. 123(12): e2517118123

Reprogrammed SimCells for antimicrobial therapy.

Yun Dong, Xianglin Ji, Tao Dong, Yun Wang, Erik Bakkeren, Kevin R Foster, Wei E Huang.

  Antimicrobial resistance (AMR) is a critical global health challenge. In this study, we developed a platform based on chromosome-free and nonreplicating simple cells (SimCells, size 1 to 2 µm) and mini-SimCells (size 100 to 400 nm) for targeted pathogen elimination. Engineered with surface-displayed nanobodies, SimCells and mini-SimCells selectively bind bacteria expressing specific antigens (e.g., OmpA in Escherichia coli). The selective interactions facilitate close SimCell-pathogen proximity, enabling two antimicrobial mechanisms: direct injection of toxic effectors into bacterial cytoplasm via a heterologous expression of type VI secretion system (T6SS), and enzymatic conversion of aspirin into catechol by engineered salicylate hydroxylase, leading to sustained local production of hydrogen peroxide (H2O2). Our results demonstrate that both reprogrammed SimCells and mini-SimCells can eliminate target E. coli with high specificity and efficiency. Multidose reprogrammed mini-SimCell treatment led to a 103-fold selective reduction of targeted bacteria in mixed microbial communities, with minimal disruption to nontarget bacteria. We demonstrate that reprogrammed mini-SimCells, engineered with nanobody targeting outer membrane protein OmpA of the clinically relevant multidrug-resistant pathogen E. coli ST131, achieved elimination efficiencies over 97% at 24 and 48 h. This modularized "plug-and-play" antimicrobial platform provides a highly specific, efficient, and adaptable solution for combating diverse AMR pathogens.

Keywords:  AMR; SimCells; nanobody; synthetic biology; therapy

DOI:  https://doi.org/10.1073/pnas.2517118123
Nat Biotechnol. 2026 Mar 18.

Precise, minimally evolved adenine base editors generated through mutation reversion analysis.

Mallory Evanoff, Sanjana Korpal, Zachary D Krill, Quinn T Cowan, Alexis C Komor.

The initial development of adenine base editors (ABEs), which facilitate A•T to G•C base pair changes in the genome, used directed evolution to install 14 mutations into the wild-type deaminase TadA, producing the first-of-its-kind editor ABE7.10. Here we study the installed mutations' impacts on TadA fitness using comprehensive reversion analysis and apply our results to engineer more efficient, precise editors. By measuring activity in both human and Escherichia coli host systems, we categorize mutations as critical, dispensable or host dependent. We show that up to five mutations can be reverted back to wild type, generating minimally evolved ABEs (ME-ABEs). ME-ABEs show narrow editing windows (similar to that of ABE7.10) and enhanced on-target editing (matching activities of the high-activity editor variants ABE8e and ABE8.20 in most sequence contexts) and exhibit low levels of guide-RNA-dependent and guide-RNA-independent off-target activity. ME-ABEs efficiently target six sites of clinical interest that had previously proved challenging to edit with ABE7.10, ABE8e or ABE8.20.

DOI: https://doi.org/10.1038/s41587-026-03045-z