bims-enlima Biomed News
on Engineered living materials
Issue of 2026–04–26
23 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool
  1. DNA Condensates Enable Crosstalk-Free Operation of Identical DNA Computing Cascades.
  2. Bio-inspired 3D-printed earthen materials and structures.
  3. De novo chemo-optogenetics through the rational design of photoresponsive molecules and selection of their artificial protein binding pairs.
  4. Designing soft materials through synthetic morphogenesis.
  5. Photosynthetic engineered living materials incorporating recombinant Chlamydomonas reinhardtii enable long-term semi-continuous photobiotransformation.
  6. Superstrong and supertough biomimetic nanocellulose composites with gradient bouligand architecture.
  7. Synthetic mechanobiology.
  8. Rotational 3D printing of active-passive filaments and lattices with programmable shape morphing.
  9. Printable Conductive Hydrogels for Electrochemical Biosensing and Soft Bioelectronic Interfaces.
  10. Multimaterial Digital Light Processing 3D Printing of Self-Sensing and Thermoresponsive Soft Actuators.
  11. Improving photosynthesis by scattering hydrogel fiber-enabled volumetric illumination.
  12. Nanoengineering conductive soft interfaces for electrogenic cell interactions: a review of materials, fabrication and functionalisation strategies.
  13. To bioprint morphogenic organoids it is essential to chill out and relax.
  14. pCODE tRNA Expression Plasmids Compensate for Rare Codons in Recombinant Protein Production.
  15. Cell shapes decode molecular phenotypes in image-based spatial proteomics.
  16. Reprogrammable shape memory ion gels via physical entanglement of ultrahigh molecular weight polymers.
  17. Designing multi-site charge-bifurcation networks in de novo proteins: a kinetic, statistical, and machine-learning approach.
  18. Light-activated cartilage decellularised extracellular matrix hydrogels for engineering chondrogenic microenvironments with localised oxygen control.
  19. Live-shaping of hydrogel thin films with light.
  20. Fast analysis and engineering of protein function by microbe-independent deep assembly and screening.
  21. Patterns of mitochondrial ATP predict tissue folding.
  22. SIGMA: Shear-induced gelation by microbead aggregation in tubular flow systems.
  23. Piezo1-mediated mechanohydraulic control of cell volume drives cardiac morphogenesis.
  1. Angew Chem Int Ed Engl. 2026 Apr 20. e5954994
    DNA Condensates Enable Crosstalk-Free Operation of Identical DNA Computing Cascades.
    Weixiang Chen, Rahmetullah Demirci, Miao Xie, Andreas Walther.
      DNA strand displacement reactions (SDR) have enabled the development of biosensing devices, molecular machines, and molecular computing. However, the need for high sequence orthogonality poses a major challenge to the modular integration and scaling of DNA SDR networks into more complex systems capable of advanced or parallel functions. Here, we propose the use of liquid-like DNA condensates with addressable barcodes for confining DNA SDR networks for parallel and selective operation of near-identical circuits that would otherwise show undesired crosstalk in a homogeneous solution. By introducing Transducer modules, specific inputs can be recognized by corresponding condensates and converted to a unified Messenger for triggering downstream DNA processing locally. This allows orthogonal execution of DNA SDRs of the same sequence design in different compartments in parallel without crosstalk and interference. Our strategy contributes a facile approach to enhance modularity and scalability in DNA SDR network design, paving the way for more sophisticated and complex functionalities.
    Keywords:  DNA computing; DNA condensates; DNA nanotechnology; supramolecular chemistry; systems chemistry
    DOI:  https://doi.org/10.1002/anie.5954994
  2. Nat Commun. 2026 Apr 18.
    Bio-inspired 3D-printed earthen materials and structures.
    Samuel J Armistead, Yierfan Maierdan, Olga B Carcassi, Rebecca A Mikofsky, Shiho Kawashima, Lola Ben-Alon, Wil V Srubar Iii.
      Nature provides a powerful blueprint for fabricating high-performance 3D-printed earthen materials and structures, such as termite mounds, wasp nests, and honeycomb worm reefs. However, mimicking the chemical and biological building blocks nature employs remains largely unexplored at scale. Here, we introduce a multiscale, bio-inspired approach that optimizes physicochemical interactions between biopolymers and earthen minerals at the microscale and systematically scales preferred interactions across spatial dimensions to fabricate macroscale, high-performance, 3D-printed earthen structures. By analyzing 90% of global subsoil minerals, we established a universally applicable multiscale optimization pathway, which converged on an alginate-based biopolymer-stabilizer that increases printing speeds by 33% and structural stability by 10° in architecturally relevant structures. This discovery accelerates the development of more efficient, resilient, and complex 3D-printed earthen structures, paving the way for sustainable, high-performance construction in the 21st century.
    DOI:  https://doi.org/10.1038/s41467-026-71885-z
  3. Nat Chem. 2026 Apr 23.
    De novo chemo-optogenetics through the rational design of photoresponsive molecules and selection of their artificial protein binding pairs.
    Tomoki Miyazaki, Tomoshige Fujino, Tatsuyuki Yoshii, Haruto Kosugi, Mamoru Funane, Naoya Murata, Kim Chung Nguyen, Satoru Nagatoishi, Kouhei Tsumoto, Gosuke Hayashi, Hiroshi Murakami, Shinya Tsukiji.
      Optical manipulation of proteins is central to probing and engineering cellular functions. However, existing optogenetic tools based on natural photoreceptors and chemo-optogenetic tools based on natural protein-ligand pairs are difficult to reconfigure for the desired photochemical and binding properties. Here we introduce a de novo approach for creating chemo-optogenetic tools. Instead of modifying pre-existing ligands, we first design a synthetic photoswitch with defined properties and then use mRNA display to select for artificial protein binders that recognize a specific photoisomer-dependent conformation. This bottom-up framework yields artificial photoswitch-protein binder pairs that enable precise optical control of diverse biological activities in mammalian cells, such as kinase and lipid signalling, G-protein-coupled receptor activation, gene expression and cell differentiation. The regulatory mode (sustained, reversible or repeatable) is readily programmed by adjusting light inputs. This de novo approach provides customizable synthetic photoswitch-protein binder pairs, expanding opportunities for optical protein manipulation in biological and biomedical applications.
    DOI:  https://doi.org/10.1038/s41557-026-02121-w
  4. Nat Commun. 2026 Apr 21.
    Designing soft materials through synthetic morphogenesis.
    Evgeniy O Bortnikov, Arpita Paikar, Ekaterina A Zhigileva, Polina Fomitskaya, Noam Ariel, Yael Diskin-Posner, Liat Avram, Xiao-Meng Sui, Ekaterina V Skorb, István Sütő, Dezső Horváth, Ágota Tóth, Sergey N Semenov.
      While the principles of Turing-type morphogenesis are central to understanding biological pattern formation, their rational application for the design of synthetic materials remains a significant challenge. To address this gap, we rationally design stationary reaction-diffusion patterns using a chemical reaction network (CRN) of small organic molecules bearing thiol groups - a functional handle ubiquitous in materials chemistry. The CRN features autocatalysis coupled with both rapid direct inhibition and a negative feedback loop. We report the formation of dot, line, and net patterns obtained with the assistance of numerical modeling by adjusting reactant feed rates and concentrations. The use of disulfide-crosslinked polyacrylamide hydrogels enables the modulation of thiol diffusion and subsequent derivatization of the immobilized thiols with dyes, enzymes, and crosslinkers to produce soft materials. This entire process, from out-of-equilibrium self-organization to a patterned soft material, conceptually resembles the biological process that gives rise to skin patterns. Overall, this work establishes a pathway for applying Turing-type self-organization to the structuring of synthetic matter.
    DOI:  https://doi.org/10.1038/s41467-026-71999-4
  5. N Biotechnol. 2026 Apr 21. pii: S1871-6784(26)00050-6. [Epub ahead of print]
    Photosynthetic engineered living materials incorporating recombinant Chlamydomonas reinhardtii enable long-term semi-continuous photobiotransformation.
    Vilja Siitonen, Tiia Siivola, Pornpan Napaumpaiporn, Tekla Tammelin, Yagut Allahverdiyeva.
      Photosynthetic engineered living materials (ELMs) present an attractive platform for producing valuable compounds and fuels using solar energy. Compared to traditional suspension cultures, ELMs enable long-term biocatalytic activity, more efficient light utilization, and facilitate downstream processing. In this study, we developed photosynthetic ELMs by entrapping Chlamydomonas reinhardtii in either alginate or TEMPO-oxidized cellulose nanofibers (TCNF). The strain utilized was converting cyclohexanone to ε-caprolactone via photobiotransformation. The cell loading and matrix material were evaluated in short-term reactions and during a semi-continuous bioproduction in vials. We showed that the entrapped cells remain photosynthetically active and catalytically competent over extended periods. By replenishing the substrate and collecting the product every 24hours we achieved semi-continuous photobiotransformation for over two weeks, reaching an average productivity of 2.31 ± 0.26gm-2 d-1 and accumulating 0.31 ± 0.03molm-2 corresponding to 3.49 ± 0.31gL-1 of ε-caprolactone. These findings establish photosynthetic ELMs as a viable approach for long-term whole-cell photobiotransformation.
    Keywords:  Alginate; Baeyer-Villiger monooxygenase BVMO; Chlamydomonas reinhardtii; Cyclohexanone monooxygenase (CHMO); TEMPO-oxidized cellulose nanofibers (TCNF); engineered living materials; immobilization
    DOI:  https://doi.org/10.1016/j.nbt.2026.04.004
  6. Nat Commun. 2026 Apr 23.
    Superstrong and supertough biomimetic nanocellulose composites with gradient bouligand architecture.
    Qi Wang, Bentao Wu, Shudong Yu, Rui Xiong.
      Lightweight structural materials with high strength and multifunctionality are urgently needed for advanced applications in aerospace, automotive, and sustainable engineering. However, conventional composites often suffer from limited mechanical performance, anisotropic mechanical behavior, or non-sustainable resource. Inspired by the Bouligand structure found in arthropod cuticles, we report a scalable approach for fabricating high-performance nanocellulose composites with a biomimetic gradient helical organization. By employing a programmable assembly process involving aligned cellulose nanofiber layers and an optimized interfacial matrix, we successfully constructed a dense, macroscopically isotropic bulk material. The multi-level hierarchical design promotes efficient energy dissipation through mechanisms such as microcrack deflection, interlayer sliding, and dynamic hydrogen bonding across scales. As a result, the composites exhibit outstanding mechanical performance, achieving a tensile strength of 649.9 MPa, fracture toughness of 192.1 MJ·m-3, and puncture resistance of 178.4 N/mm-values that substantially exceed those of leading natural and synthetic structural counterparts. Moreover, the material demonstrates multifunctional characteristics, including tunable structural coloration, effective electromagnetic interference shielding, and exceptional stability across extreme temperatures. This work establishes a versatile and sustainable platform for the development of advanced structural materials suited for demanding environments such as spacecraft shielding, robotic systems, and next-generation vehicular technologies.
    DOI:  https://doi.org/10.1038/s41467-026-72343-6
  7. Curr Biol. 2026 Apr 20. pii: S0960-9822(26)00292-7. [Epub ahead of print]36(8): R309-R317
    Synthetic mechanobiology.
    John T Ngo.
      Cells do not simply endure mechanical forces - they generate, transmit, and interpret them as biological signals. From membrane tension and receptor pulling to substrate stiffness and fluid shear, physical inputs shape migration, differentiation, immune function, and tissue organization. Whereas mechanobiology seeks to understand how living systems read these cues, synthetic mechanobiology treats mechanoregulatory pathways as an input-output relationship that can be deliberately programmed. Integrating tools from synthetic biology with mechanobiological principles, this emerging field reframes force-sensing as a design problem in which mechanical signaling is rewired to achieve useful outcomes - and in which the act of rewiring can itself serve as a powerful investigational strategy. Here, I survey the molecular mechanisms of mechanosensing, describe their use as modular mechanogenetic parts, and discuss applications and open challenges. The long-term vision is to build engineered cells that not only read tissue mechanics but act on them, turning the physical signatures of disease into precise, locally delivered therapeutic programs.
    DOI:  https://doi.org/10.1016/j.cub.2026.03.005
  8. Proc Natl Acad Sci U S A. 2026 Apr 28. 123(17): e2537250123
    Rotational 3D printing of active-passive filaments and lattices with programmable shape morphing.
    Mustafa K Abdelrahman, Jackson K Wilt, Yeonsu Jung, Rodrigo Telles, Gurminder K Paink, Natalie M Larson, Joanna Aizenberg, L Mahadevan, Jennifer A Lewis.
      Natural filaments, such as proteins, plant tendrils, octopus tentacles, and elephant trunks, can transform into arbitrary three-dimensional shapes that carry out vital functions. Their shape-morphing behavior arises from intricate patterning of active and passive regions, which are difficult to replicate in synthetic matter. Here, we introduce a filament-centric strategy for programmable shape morphing in which intrinsic curvature and twist are directly encoded within multimaterial elastomeric filaments during fabrication. By harnessing rotational multimaterial 3D printing, we directly prescribe the filament's natural curvature-twist field κ(s) through controlled material distribution and helical liquid crystal mesogen alignment. When heated above their nematic-to-isotropic transition temperature (TNI), the helically aligned liquid crystal elastomer regions contract along their local director field, while passive regions remain essentially unchanged. This approach enables independent control of bending and torsion at every cross-section along the filament centerline: the principal natural curvatures of the filament along two orthogonal axes as well as the local twist. Next, we printed architected lattices composed of unit cells formed by sinusoidal filaments that either reversibly contract, expand, or exhibit out-of-plane deformations. Discrete elastic rod simulations of Janus filaments with different natural curvatures and twist, which are interconnected within the printed lattices, allow accurate prediction of their observed shape-morphing behavior. By integrating active-passive elastomers, additive manufacturing, and computational modeling, we have created shape-morphing matter with complex programmable responses for applications that rely on adaptive, robotic, or deployable architectures.
    Keywords:  liquid crystal elastomers; rotational 3D printing; shape morphing
    DOI:  https://doi.org/10.1073/pnas.2537250123
  9. Adv Sci (Weinh). 2026 Apr 23. e21216
    Printable Conductive Hydrogels for Electrochemical Biosensing and Soft Bioelectronic Interfaces.
    Lukas Hein, Renan Colucci, Xin Wei, Tsvetomir Ivanov, Katharina Landfester, Ulrike Kraft, Maria Villiou.
      The development of flexible, conductive biomaterials is key to advancing next-generation biosensors and wearable health monitoring systems. However, combining printability, mechanical tunability, biocompatibility, and electronic performance within a single hydrogel remains a significant challenge. Here, we present a facile method to fabricate biofunctional conducting poly(ethylene glycol)-poly(pyrrole) (PEG-PPy) hydrogels via 3D-printing. The soft and flexible PEG-PPy hydrogels feature tunable mechanical properties and can be easily loaded with bioreceptors, enabling integration into sensing platforms. The composite consists of a poly(ethylene glycol) diacrylate matrix and a conductive polypyrrole filler. By optimizing photopolymerization conditions, we enable extrusion printing of complex, multi-layered structures with excellent shape fidelity (printability ≈ 1). The resulting hydrogels exhibit tunable stiffness (15-120 kPa), high cytocompatibility (>90%), and robust mechanical integrity. Integration of the hydrogel as a gate electrode in an organic electrochemical transistor yielded transconductance values comparable to conventional Ag/AgCl gates, confirming its electrochemical performance. Furthermore, embedding glucose oxidase into the hydrogel enabled enzymatic glucose sensing over a physiologically relevant range (1-100 mm). This cost-effective, multifunctional, and versatile PEG-PPy hydrogel platform offers a scalable route toward soft, flexible, printable electronic interfaces.
    Keywords:  3d printing; conductive hydrogels; conductive polymers; gate electrodes; glucose sensors; organic electrochemical transistors (OECTs); soft bioelectronics
    DOI:  https://doi.org/10.1002/advs.202521216
  10. ACS Appl Mater Interfaces. 2026 Apr 23.
    Multimaterial Digital Light Processing 3D Printing of Self-Sensing and Thermoresponsive Soft Actuators.
    Yifei Miao, Xiaokang Liu, Shenglin Yang, Jinghong Ma.
      The potential of soft actuators for tasks in complex environments remains constrained by their lack of real-time proprioceptive capabilities. Here, this challenge is addressed through a multimaterial digital light processing (DLP) 3D printing strategy for constructing bilayer actuators integrating thermoresponsive actuation with strain-sensing functions. Two photocurable functional inks were developed and integrated into a single heterogeneous bilayer system via multimaterial DLP 3D printing. The passive layer consists of a dual-network ionoelastomer based on a polymerizable deep eutectic solvent (PDES) and carboxymethyl cellulose (CMC), with favorable mechanical properties (tensile strength ∼0.5 MPa) and sensitive strain-sensing performance (gauge factor = 2.11). The active layer is composed of a functionalized poly(N-isopropylacrylamide) hydrogel; the incorporation of a DES synergistically enhanced its mechanical performance (compressive strength ∼1.05 MPa) while enabling effective regulation of the lower critical solution temperature (LCST: 32-46 °C). Seamless integration and robust interfacial bonding between these heterogeneous materials were achieved by systematically optimizing the printing process. The resulting bilayer actuators demonstrated efficient and tunable thermoresponsive actuation, with programmable complex deformations realized through the structural design of the active layer. Furthermore, the integrated sensing capabilities enabled self-perception, allowing the actuator to monitor its own deformation states during actuation. This multimaterial DLP 3D printing strategy established a material and processing foundation for the construction of intelligent soft systems with proprioceptive capabilities.
    Keywords:  bilayer structure; deep eutectic solvents; multimaterial DLP 3D printing; programmable deformation; self-sensing; soft actuators
    DOI:  https://doi.org/10.1021/acsami.6c00142
  11. Proc Natl Acad Sci U S A. 2026 Apr 28. 123(17): e2536344123
    Improving photosynthesis by scattering hydrogel fiber-enabled volumetric illumination.
    Yijie Cheng, Mohamed A Elhabet, Akhiri Zannat, Lenan Zhang, Xuanjie Wang, Yuchen Bian, Siyuan Rao, Yan Liu, Wei Liao, Yoichiro Tsurimaki, Xinyue Liu.
      Photosynthetic biomanufacturing offers a sustainable route to generate valuable bioproducts by harnessing microorganisms such as algae to convert sunlight and carbon dioxide into biomass. A major barrier to efficient production is that light penetrates poorly into dense algal cultures, restricting photosynthesis to a thin surface layer and severely limiting the solar energy that can be utilized for algal growth and biomass production. Here, we present a material-based strategy to overcome this fundamental bottleneck by deploying bulk-scattering, index-matched optical fibers that redistribute sunlight uniformly throughout the culture volume. These fibers are made from amorphous hydrogels with a refractive index closely matched to that of algal media and contain scattering nanoparticles that redirect light to achieve volumetric illumination. When integrated into solar-powered algal systems, the fibers enable dense and sustained algal growth at 0.8 to 1.4 g L-1 over 2 mo of semicontinuous outdoor cultivation, resulting in volumetric biomass productivity of 0.15 g L-1 day-1 and photosynthetic efficiency of 1.4%, significantly higher compared to algal systems without fibers. This study demonstrates the transformative potential of optical modulation to the long-standing low productivity in dense algal culture, providing a scalable, sustainable, and efficient pathway for solar-driven biomanufacturing.
    Keywords:  hydrogel fiber; light management; photosynthesis
    DOI:  https://doi.org/10.1073/pnas.2536344123
  12. Biofabrication. 2026 Apr 22.
    Nanoengineering conductive soft interfaces for electrogenic cell interactions: a review of materials, fabrication and functionalisation strategies.
    Bin Guan, Jessica de la Perrelle, Jing Zhang, Rhys John Tunnadine, Mansi Malik, Ruiping Li, Rebecca Lim, Matthew J Griffith.
      Conductive soft materials are emerging as critical platforms for interfacing with electrogenic cells, such as neurons and cardiomyocytes. Unlike rigid metal electrodes, these materials offer tuneable conductivity for reliable electrical communication, tissue-like softness for mechanical compliance, and chemical or bioactive functionalities for effective integration with biological systems. However, achieving an optimal balance between conductivity, mechanical properties, and biocompatibility remains a significant challenge that is strongly dependent on the fabrication pathway selected. The array of advanced biofabrication methodologies continues to expand rapidly, enabling "top down" approaches that start with bulk materials or "bottom up" approaches that enable more precise formation of structures from molecular building blocks. To equip researchers with a practical toolkit for selecting application-specific materials and designing effective bio-interfaces in areas such as neuroengineering and cardiac modelling, here we provide a comprehensive review of fabrication and functionalisation strategies for these materials. We first introduce some key classes of conductive soft materials, highlighting their unique properties when interacting with electrogenic cells. Fabrication techniques, including spin-coating, electrospinning, moulding, lithography, and 3D printing, are then examined, with a focus on identifying their strengths and limitations in the context of specific bioelectronic applications. Finally, strategies for tailoring post-fabrication surface chemistry to enhance cell interaction and growth are discussed. In the final section, emerging opportunities and future directions for conductive soft interfaces are highlighted.
    Keywords:  Biofabrication; Neuroengineering; Organic Electronics; Polymers; Soft Materials; bioelectronics; functional materials
    DOI:  https://doi.org/10.1088/1758-5090/ae6370
  13. Nat Mater. 2026 Apr 23.
    To bioprint morphogenic organoids it is essential to chill out and relax.
    Christopher B Highley, Thomas E Angelini.
      
    DOI:  https://doi.org/10.1038/s41563-026-02581-y
  14. ACS Synth Biol. 2026 Apr 21.
    pCODE tRNA Expression Plasmids Compensate for Rare Codons in Recombinant Protein Production.
    Marilena Feller, Ana G V Sepulchro, Maurice Mürköster, Daniel O Daley, Alexandros Karyolaimos, Sheila I Jensen, Morten H H Nørholm.
      The molecular mechanisms that constrain recombinant protein production and the importance of synonymous codon usage have not been fully elucidated. Codon frequency varies between different organisms, and rare codons are often avoided in "codon-optimized" synthetic gene constructs. Overexpression of tRNA genes is an alternative strategy to compensate for suboptimal codon usage, but the consequences and limitations of this approach have not been widely studied. Here, we develop and characterize a versatile collection of pCODE plasmids for tRNA overexpression in Escherichia coli and show that they complement rare codons with very modest limitations or negative effects, regardless of the position, type, number, or distribution of rare codons in the expressed gene. One pCODE plasmid encodes an inducible tRNA expression cassette and shows potential as a new type of genetic regulation based on inducible rare codon complementation. The pCODE tRNA expression plasmids provide mechanistic insights into synonymous codon usage and add to the molecular biology toolbox that enables recombinant protein production.
    Keywords:  Escherichia coli; GFP; codon optimization; recombinant protein production; tRNA expression; transcription
    DOI:  https://doi.org/10.1021/acssynbio.5c00794
  15. Cell Syst. 2026 Apr 20. pii: S2405-4712(26)00071-2. [Epub ahead of print] 101589
    Cell shapes decode molecular phenotypes in image-based spatial proteomics.
    Trang Le, William D Leineweber, Matheus P Viana, Anthony Cesnik, Jan N Hansen, Wei Ouyang, Susanne M Rafelski, Emma Lundberg.
      Cellular and tissue structures arise from a few cell shapes, which undergo transformations based on biophysical constraints. Despite links between signaling pathways and cellular geometry, whole-proteome orchestration in association with cell shape is underexplored. In this study, over 1 million single cells stained for 11,998 proteins across 11 cell lines in the Human Protein Atlas were analyzed for organelle, pathway, and single-protein levels in association with cellular shapespace. We found that cell and nuclear shapes across cell lines exist in a shared continuum. The subcellular organelle topology varies across cell lines but remains consistent within each cell line's shapespace. At the single-protein level, cells of different shapes in the same cell-cycle phase might be preparing for different fates, and many non-cell-cycle proteins expressed shape-based abundance variation. Using a shape-based coordinate framework, we analyzed the distribution shift of protein spatial localization under drug perturbation.
    Keywords:  cell shape; interpretable machine learning; molecular variation; morphological variation; single cell; spatial proteomics
    DOI:  https://doi.org/10.1016/j.cels.2026.101589
  16. Mater Horiz. 2026 Apr 20.
    Reprogrammable shape memory ion gels via physical entanglement of ultrahigh molecular weight polymers.
    Ryota Tamate, Koichiro Uto, Yuji Kamiyama, Takeshi Ueki.
      In this study, we develop shape memory ion gels comprising ultrahigh molecular weight (UHMW) polymers and ionic liquids (ILs), synthesised via a facile one-pot radical polymerisation method of vinyl monomers in the IL medium. The resulting ion gels exhibit a high glass transition temperature (Tg) above room temperature and a broad rubbery plateau, attributed to the abundant physical entanglements of the UHMW polymers in the IL medium. Dynamic mechanical analysis confirms their excellent shape-memory performance, including triple shape-memory behaviour. By leveraging the nonvolatility of IL, the ion gels can be recycled through thermal remoulding with minimal degradation in their mechanical properties. Furthermore, they retain their shape-memory performance over multiple deformation cycles with negligible residual strain, in contrast to their counterparts containing lower molecular weight polymers, which suffer from chain pullout and incomplete recovery. Notably, this study demonstrates that densely entangled polymer networks can enable shape reprogramming, highlighting physical entanglements as a robust and dynamic cross-linking motif. Moreover, the Tg can be finely tuned by adjusting the polymer/IL composition or by selecting different IL structures, offering a versatile strategy for designing high-performance shape memory materials.
    DOI:  https://doi.org/10.1039/d5mh01902h
  17. Phys Chem Chem Phys. 2026 Apr 22.
    Designing multi-site charge-bifurcation networks in de novo proteins: a kinetic, statistical, and machine-learning approach.
    Xiao Huang, William F DeGrado, Michael J Therien, David N Beratan.
      Electron bifurcation reactions separate electron pairs into high and low potential pools, and these reactions are central to the bioenergetics of living systems. Here, we used kinetic analysis and machine learning to analyze a diverse set of structural and electrochemical landscapes that may guide the design of molecular architectures that could serve as experimental targets that would function to bifurcate holes using light. We find that strong electrostatic repulsion between the holes enhances the quantum yield for bifurcation but reduces the energy efficiency of the process. We find that the quantum yield for hole bifurcation is enhanced by positioning the hot-hole pathway cofactor farther from the hole bifurcation site than its cold-hole pathway counterpart. This integrated design and optimization approach provides design strategies for de novo structures that could realize light-drive hole bifurcation, advancing the aim of employing bioinspired electron bifurcation for energy conversion, photocatalysis, and electrocatalysis. Beyond the specific light-driven hole-bifurcation architecture, our combined kinetic-statistical-machine-learning approach is transferable to other multi-particle, multi-site charge-transport network design challenges, opening paths for designing photochemical and catalytic networks, as well as for designing functional redox networks.
    DOI:  https://doi.org/10.1039/d6cp00473c
  18. Biofabrication. 2026 Apr 20.
    Light-activated cartilage decellularised extracellular matrix hydrogels for engineering chondrogenic microenvironments with localised oxygen control.
    Lin Li, Louis Jun Ye Ong, Khoon S Lim, Chamikara Dushmantha Kaluthara Liyanage, Yunkun Qu, Jingyi Wen, Caitlin Williams, Thomas G Molley, Roberto A Barrero, Shital Wakale, Ross Crawford, Kristopher Kilian, Yi-Chin Toh, Indira Prasadam.
      Cartilage tissue engineering requires biomaterials that can effectively maintain the tissue-specific functions of chondrocytes to enable the restoration of cartilage structure and function. Decellularised extracellular matrix (dECM)-derived hydrogels serve as tissue-specific biomaterials capable of preserving native biochemical cues and maintaining physiological chondrocyte phenotype in three-dimensional culture. However, their sol-gel transition relies heavily on collagen fibrillogenesis, a slow and poorly controllable process that limits mechanical tunability and suffers from inter-batch variability. Therefore, further efforts are required to functionalise cartilage dECM to achieve reproducible and controllable physicochemical properties. Here, we present a light-activated cartilage dECM hydrogel system based on ruthenium/sodium persulfate (Ru/SPS)-mediated dityrosine crosslinking, enabling rapid hydrogel formation under visible light irradiation while providing tunable mechanical properties and improved biological functionality. Comparison of the decellularisation protocols indicated that Triton X-100 combined with ammonium hydroxide efficiently eliminated residual DNA while preserving a substantial proportion of the native cartilage proteome. Pepsin-solubilised cartilage dECM hydrogels formed via dityrosine-based photo-crosslinking exhibited rapid gelation behaviour and superior mechanical characteristics compared to conventional thermally gelled dECM. The photo-crosslinked dECM hydrogels were cytocompatible, supported human bone marrow-derived mesenchymal stem cells (hBMSCs), and favoured cartilage-specific phenotypes, as demonstrated by chondrogenic genes upregulation, including COL2A1 and ACAN, compared with gelatin methacrylate (GelMA) hydrogels. Importantly, this photo-crosslinking strategy overcomes the incompatibility between oxygen-sensitive redox-based photochemistry and hypoxic culture conditions, enabling the incorporation of oxygen-scavenging microcapsules to establish low-oxygen microenvironments. Under hypoxia, the cartilage dECM hydrogels promoted a more articular-like phenotype in hBMSC-derived chondrocytes, with transcriptomic features associated with TGF-β/SMAD2/3 and IGF-1/2-IGF-1R signalling. Collectively, these findings establish photo-crosslinked cartilage dECM hydrogels as a biomaterial platform with tunable mechanical properties and favourable biological functionality for cartilage tissue bioengineering and biomimetic in vitro cartilage models.
    Keywords:  Chondrogenic differentiation; Decellularised cartilage extracellular matrix; Hypoxia; Photo-crosslinked hydrogel; hBMSC
    DOI:  https://doi.org/10.1088/1758-5090/ae61f5
  19. Nat Commun. 2026 Apr 21. pii: 3613. [Epub ahead of print]17(1):
    Live-shaping of hydrogel thin films with light.
    Matias Paatelainen, Henning Meteling, Alex Berdin, Arri Priimagi.
      Light-responsive hydrogels are attractive materials for mimicking dynamic microstructures in nature, providing platform for tunable devices in photonics, sensing, and biomedicine. However, these systems often suffer from limited spatial resolution and slow response times, restricting their utility in high-speed or high-precision applications. Here, we present a light-responsive hydrogel thin film platform capable of rapid, reconfigurable surface modulation with sub-micron spatial resolution and actuation frequencies up to 2 Hz. The system leverages photoswitchable host-guest interactions to induce reversible contraction-expansion in response to patterned illumination. Dual-wavelength control enables the generation of dynamic, migrating surface features capable of transporting micro-objects in real time. The approach is further extended to free-standing films, demonstrating functionality in laser beam steering. Additionally, surface patterns can be stabilized by drying and erased by humidity, offering a route to rewritable sensor tags.
    DOI:  https://doi.org/10.1038/s41467-026-71438-4
  20. Mol Syst Biol. 2026 Apr 23.
    Fast analysis and engineering of protein function by microbe-independent deep assembly and screening.
    Yan Wu, Pengli Wang, Lan Xiang Liu, Daesun Song, Qin Qin, Chao Gao, Matt Hageman, Thomas A Kirkland, Yichi Su, Michael Z Lin.
      Traditional methods for engineering and sequence-fitness analysis of proteins in mammalian cells are limited by the time, cost, and labor associated with plasmid cloning and preparation. Here we present Microbe-Independent Deep Assembly and Screening (MIDAS), a deterministic platform for rapid protein variant expression and characterization in mammalian cells that bypasses microbial cloning by directly transfecting PCR-assembled genes. MIDAS enables high-quality sequence-fitness assessment of arbitrary mutational spaces, including truly deep saturation mutagenesis and combinatorial variant assembly, requiring less than one workday from initial PCR to cell transfection. Using MIDAS, we engineer a high-performance acetylcholine neurotransmitter bioluminescent indicator (ACh-NeuBI), achieving stepwise improvements in responsivity through linker engineering, single-site, and multi-site mutagenesis. We also apply MIDAS to engineer improved NanoLuc luciferase variants for multiple substrates, and to characterize the structural basis of mutational tolerance and substrate specificity. Thus, MIDAS is a versatile method for rapid plasmid-free protein engineering and sequence-fitness analysis in mammalian cells, offering a practical alternative to cloning-based approaches for many protein optimization and characterization tasks.
    DOI:  https://doi.org/10.1038/s44320-026-00210-z
  21. Sci Adv. 2026 Apr 24. 12(17): eaee6175
    Patterns of mitochondrial ATP predict tissue folding.
    Bezia Lemma, Megan Rothstein, Pengfei Zhang, Bridget Waas, Marcus Kilwein, Safiya Topiwala, Sherry X Zhang, Anvitha Sudhakar, Katharine Goodwin, Elizabeth R Gavis, Ricardo Mallarino, Andrej Kosmrlj, Celeste M Nelson.
      The construction of tissue shapes during embryonic development results from patterns of gene expression and mechanical forces fueled by chemical energy from ATP hydrolysis. We find that chemical energy is similarly patterned during apical constriction, which is widely used across the animal kingdom to fold epithelial tissues. Time-lapse imaging, spatial transcriptomics, and measurements of oxygen consumption rate reveal that mitochondrial density, potential, and ATP increase at the apical side of epithelial cells before actomyosin contraction and tissue folding, which is prevented by inhibiting oxidative phosphorylation. Mitochondrial enrichment and apical bias are conserved during apical constriction in flies, chicks, and mice, and these patterns can be used to predict computationally patterns of tissue folding. These findings highlight a spatial dimension of bioenergetics in development.
    DOI:  https://doi.org/10.1126/sciadv.aee6175
  22. Mater Today Bio. 2026 Jun;38 103120
    SIGMA: Shear-induced gelation by microbead aggregation in tubular flow systems.
    Yu Ri Nam, Yeongjin Lee, Keumyeon Kim, Jeongin Seo, Jeehee Lee, Hee-Seung Lee, Haeshin Lee.
      Injectable hydrogels hold promise for localized drug delivery and regenerative medicine, yet their clinical translation remains limited by reliance on backbone modification or exogenous physicochemical triggers that complicate delivery. Here, we exploit an unavoidable aspect of clinical administration, shear, which is generated during injection through catheters and needles. We introduce SIGMA (Shear-Induced Gelation by Microbead Aggregation), a system composed of gelatin microbeads that remain flowable during injection but rapidly assemble into cohesive hydrogel under confined shear, without exogenous physicochemical triggers such as temperature, pH, light, or chemical crosslinkers. Gelation was tunable by varying flow path length, mixing cycles, particle sizes, or introducing air-liquid interfaces, enabling transitions from a weak dispersion (∼11.3 Pa) to robust gels with storage moduli up to ∼5 kPa and compressive strengths approaching ∼800 kPa. Circular dichroism and gel permeation chromatography revealed shear-induced intermolecular associations without evidence of chain scissions. The platform further enabled post-encapsulation drug loading with tunable release governed by shear-programmed network density. In vitro and in vivo studies confirmed cytocompatibility, biodegradability, systemic safety, and superior submucosal lift compared with saline. Together, SIGMA establishes a mechanically actuated, clinically adaptable hydrogel platform for minimally invasive surgery and localized drug delivery.
    Keywords:  Gelatin microbeads; In situ gelation; Injectable hydrogel; Shear-induced gelation
    DOI:  https://doi.org/10.1016/j.mtbio.2026.103120
  23. Sci Adv. 2026 Apr 24. 12(17): eaea7025
    Piezo1-mediated mechanohydraulic control of cell volume drives cardiac morphogenesis.
    Christina Vagena-Pantoula, Konstantinos Kalyviotis, Shuyi Feng, Antoine Sanchez, Igor Kondrychyn, Moe Fukumoto, Xiangbin Pan, Thomas Juan, Didier Y R Stainier, Periklis Pantazis, Li-Kun Phng, Julien Vermot.
      Organ morphogenesis is driven by physical forces, yet how mechanical stimuli pattern tissue shape and guide developmental programs remains poorly understood. In zebrafish, endocardial cells (EdCs) within the heart valve-forming region undergo marked volume reduction during early morphogenesis. Here, we uncover a hydraulics-based mechanism by which mechanical forces control EdC volume to direct cardiac development. We show that the mechanosensitive ion channel Piezo1 acts with the calcium-binding protein calmodulin (CaM) and the aquaporin Aqp8a.1 water channel to orchestrate EdC shrinkage. We find that Aqp8a.1 mediates cell volume loss by incorporating into the plasma membrane in response to mechanical stimulation, promoting heart looping and valve formation. Mechanistically, Piezo1 governs Aqp8a.1 through a dual mechanism. First, Piezo1 and CaM drive Aqp8a.1 plasma membrane incorporation, enabling rapid cell volume adjustments. Second, Piezo1 suppresses aqp8a.1 transcription via Notch1b signaling to prevent excessive shrinkage. Together, these findings reveal that mechanotransduction can dictate organ formation through dynamic cell volume regulation, uncovering a fundamental principle of morphogenesis.
    DOI:  https://doi.org/10.1126/sciadv.aea7025
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