bims-enlima 2025-11-23 papers

bims-enlima

Biomed News

on Engineered living materials

Issue of 2025–11–23
38 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool

Nature-Inspired Living Materials for Health, Energy, and Sustainability.
Bacterial cooperative weaves sustainable rainbow materials.
Spatial Photopatterning of Substrate Stiffness in Dual-Cure Silicones for Cardiac Mechano-Regulation.
3D Bioprinted Engineered Living Microreactors for Continuous Organophosphorus Compound Degradation.
Mapping structures and dynamics with frequency-correlated diffusion exchange.
3D necroprinting: Leveraging biotic material as the nozzle for 3D printing.
Thermoplastic Molding of Chitosan to Form Living Plastic Materials.
Nano- and Microscale Chemical and Topographical Patterning of Synthetic Cell Scaffolds: from Hard to Soft Materials.
Polymer Blend Controls Nanoparticles' Surface Charge for Improved Mucus Penetration and Epithelial Cell Adhesion.
Self-Assembling Protein Materials with Genetically Programmable Morphology and Size.
Directed self-assembly of 3D interconnected networks.
Biosynthetic Polyelectrolyte Composites Exhibit Tunable Scale-Dependent Mechanics Governed by Entanglements.
Photo-excited extracellular electron transfer of electroactive microorganism triggers RAFT polymerization.
Spatially programmable origami networks enable high-density mechanical computing for autonomous robotics.
Chemical signaling in reaction networks generates corresponding mechanical impulses.
Computational design of pH-sensitive binders.
High-strength and fracture-resistant ionogels via solvent-tailored interphase cohesion in nanofibrous composite networks.
Identification and Purification of Specific Cell Populations via ADAR Editing-Driven Synthetic Genetic Circuits.
Inverse design of structural colours in polymeric films with crystallization-induced reversible thermochromism.
Multimaterial 3D Printing of Soft and Stretchable Electronics.
Electrically active hydrogels based on PEDOT:PSS for neural cultures.
Interpretable molecular decision-making with DNA-based scalable and memory-efficient tree computation.
Smart Luminescent Materials Based on Rare-Earth Complexes: From Precise Syntheses to Regulable Functions.
A crystal that breathes.
Physics-informed neural networks for programmable origami metamaterials with controlled deployment.
Generation of Cellular Biofactories for Scalable Production of Surface-Engineered Extracellular Vesicles via CRISPR Genome Editing.
Resolving the mRNA Encapsulation-Release Trade-off via Compensatory Forces in Engineered Ionizable Lipids.
Frame-Shifted Synthesis of Oligoheterocycles as a Platform for Molecular Design.
Capitalizing on mechanistic insights to power design of future-ready intracellular optogenetics tools.
Orchestrating Self-Replication in Artificial Cells with Digital Microfluidics.
A Versatile Platform for Recyclable Polyesters: Alternating Copolymerization of Aldehydes (or Their Derivatives) with Cyclic Anhydrides.
G4mer: An RNA language model for transcriptome-wide identification of G-quadruplexes and disease variants from population-scale genetic data.
Increasing the dimensionality of transistors with hydrogels.
Nature-Inspired Janus Actuators with Structurally Engineered PEDOT:PSS.
Autonomous Spatiotemporal Regulation of Reversible Hydrogel Actuators by Chemical Reaction Networks.
Light-mediated communication in responsive materials ranging from individual self-oscillators to feedback-driven network.
The open-source Masala software suite: Facilitating rapid methods development for synthetic heteropolymer design.
Sequence-encoded interactions program internal condensate architecture.

ACS Appl Bio Mater. 2025 Nov 18.

Nature-Inspired Living Materials for Health, Energy, and Sustainability.

Fanghua Li, Paolo Fornasiero, Peng Xu, Hengjia Jia, Jiazheng Xu, Haiyang Sun, Klaus Müllen, Xingcai Zhang, Kostya S Novoselov.

  Nature serves as an inexhaustible source of inspiration for advanced material design. While nature-inspired nonliving materials exhibit exceptional properties, they typically lack the dynamic functionalities of living systems, such as self-healing and environmental responsiveness. To bridge this gap, living materials, which integrate living cells (e.g., bacteria, fungi, algae) within abiotic matrices, have emerged as transformative platforms. These materials harness cellular functions (e.g., biomineralization, programmable metabolism) to achieve unprecedented adaptability and sustainability. In this review, we categorized living materials into two distinct types based on the role of the cells: (1) cells acting as platforms for material synthesis and (2) cells integrated as components of materials for functionalization. We summarized the characteristics of living and nonliving materials inspired by nature, with applications of living materials in energy, medicine, catalysis, concrete, and soft robotics. We further discussed advanced manufacturing techniques for living materials. We envision that the design principles of living materials will advance health, energy, and sustainability.

Keywords:  3D printing; advanced manufacturing; genetic engineering; living materials; microfluidics; natural materials; soft robotics; sustainability

DOI:  https://doi.org/10.1021/acsabm.5c01099
Nature. 2025 Nov 20.

Bacterial cooperative weaves sustainable rainbow materials.



Keywords:  Natural products

DOI:  https://doi.org/10.1038/d41586-025-03698-x
ACS Biomater Sci Eng. 2025 Nov 17.

Spatial Photopatterning of Substrate Stiffness in Dual-Cure Silicones for Cardiac Mechano-Regulation.

Pouria Tirgar, Luv Kishore Srivastava, José Miguel Romero Sepúlveda, Ali Amini, Amirreza Mahmoodi, Cameron Hastie, Leticia Le Goff, Allen J Ehrlicher.

  The mechanical properties of the extracellular matrix play a key role in regulating cellular functions, yet many in vitro models lack the mechanical complexity of native tissues. Traditional hydrogel-based substrates offer tunable stiffness but are often limited by instability, porosity, and coupled changes in both mechanical and structural properties, making it difficult to isolate the effects of stiffness alone. Here, we introduce a spatially patterned dual-cure polydimethylsiloxane (DC-PDMS) system, a nonporous, mechanically tunable polymer that allows for precise spatial control of stiffness over a range of patho-physiological values. This platform enables the design and creation of in vitro models for studying the influence of spatial mechanical cues on cellular behavior. To demonstrate its utility, we examined primary cardiac fibroblast responses across different substrate stiffness conditions. Fibroblasts on soft regions exhibited rounded morphologies with disorganized actin networks, while those on stiffer regions became more elongated with highly aligned stress fibers, indicating stiffness-dependent cytoskeletal remodeling. Stiff substrates also led to nuclear compression and increased nucleus curvature, correlating with increased nuclear localization of YAP, a key mechanotransduction regulator. By allowing cells to interact with mechanically distinct regions within a single substrate, this system provides a powerful approach for investigating mechanotransduction processes relevant to fibrosis and other mechanically regulated diseases. The ability to create stiffness patterns with subcellular resolution makes DC-PDMS a valuable tool for studying cell-material interactions, enabling new insights into mechanobiology-driven cellular responses and therapeutic targets.

Keywords:  PDMS; biomaterials; cardiac fibroblast activation; mechanotransduction; polymers; stiffness

DOI:  https://doi.org/10.1021/acsbiomaterials.5c01372
Small Sci. 2025 Nov;5(11): 2500226

3D Bioprinted Engineered Living Microreactors for Continuous Organophosphorus Compound Degradation.

Mark R Shannon, Graham J Day, Hermes Bloomfield-Gadêlha, Valeska P Ting, Adam W Perriman.

  Engineered living materials (ELMs) are poised to play a pivotal role in addressing critical global environmental challenges through advances in green energy production, biosensing and bioremediation. When coupled with advanced manufacturing techniques, such as 3D bioprinting, new opportunities emerge for the fabrication of high-resolution self-supporting ELM structures suitable for hosting microbial populations with bespoke chemical activity. Accordingly, the design and fabrication of a 3D bioprinted microbial ELM flow-bioreactor comprising genetically engineered Escherichia coli are described. The metabolically active ELM bioreactor cyclically detoxifies organophosphorus compounds via inducible expression of the Agrobacterium radiobacter phosphotriesterase. Principal component analysis is performed to reduce the dimensionality of the mass transfer kinetic analysis, uncovering spatiotemporal features within the dynamical evolution of the data. This provides valuable insights into the design parameters essential for the development of highly efficient catalytic microbial ELM bioreactors.

Keywords:  3D printing; biomaterials; bioreactors; bioremediation; engineered living materials; environmental biotechnology; pesticides

DOI:  https://doi.org/10.1002/smsc.202500226
Sci Adv. 2025 Nov 21. 11(47): eady8380

Mapping structures and dynamics with frequency-correlated diffusion exchange.

Sophia N Fricke, Velencia Witherspoon, Jeremy Demarteau, Brett A Helms, Jeffrey A Reimer.

Understanding molecular motion in diffusion-driven complex environments is critical for designing sustainable materials and improving chemical processes. Here, we introduce a multidimensional nuclear magnetic resonance (NMR) method that captures how molecular populations exchange across different dynamic regimes. By extending the modulated gradient spin-echo technique to include frequency-frequency correlations, our approach reveals diffusion pathways that are otherwise obscured in heterogeneous systems. Implemented on a unilateral NMR magnet, the method eliminates gradient pulsing constraints and accesses dynamics in the kilohertz regime. We apply this technique to swelling and acid-catalyzed deconstruction of cross-linked and linear polymers to observe how structural heterogeneity evolves over time. By linking molecular motion to topology and chemical state, we extract physical metrics such as fractal surface dimensionality and reaction wavefront velocity, properties inaccessible with standard diffusion measurements. This work expands the capabilities of NMR for probing soft matter, with implications for polymer recycling and materials design.

DOI: https://doi.org/10.1126/sciadv.ady8380
Sci Adv. 2025 Nov 21. 11(47): eadw9953

3D necroprinting: Leveraging biotic material as the nozzle for 3D printing.

Justin Puma, Zhen Yang, Evan Johnston, Zixin Zhang, Xiaoyi Lan, Lingzhi Zhang, Hongyu Hou, Zixin He, Ali Afify, Megan A Creighton, Jianyu Li, Changhong Cao.

Nature has long inspired engineering innovations. Recent advances in biohybrid research have taken this inspiration further by directly integrating biotic materials into engineered systems. Here we report "3D necroprinting," a biohybrid manufacturing technique that repurposes female mosquito proboscides as high-resolution 3D printing nozzles. The mosquito proboscis, with its unique geometry, structure, and mechanics, enables printed line widths as fine as 20 μm, surpassing commercially available 36-gauge dispense tips by ~100%. The mosquito proboscis dispense tip can withstand internal pressures of approximately 60 kPa, enabling effective fluid extrusion. Demonstrated applications include high-resolution printing of complex structures such as a honeycomb structure, a maple leaf, and bioscaffolds encapsulating cancer cells and red blood cells, showcasing the versatility and capacity of 3D necroprinting. By introducing biotic materials as viable substitutes to complex engineered components, this work paves the way for sustainable and innovative solutions in advanced manufacturing and microengineering.

DOI: https://doi.org/10.1126/sciadv.adw9953
Adv Mater. 2025 Nov 19. e11623

Thermoplastic Molding of Chitosan to Form Living Plastic Materials.

Reddhy Mahle, Peggy Cebe, Nilotpal Majumder, Onur Hasturk, Glenn Leung, Chunmei Li, Weiguo Hu, Edward B Gordon, Sanjana Gopalakrishnan, Yushu Wang, Sourabh Ghosh, David L Kaplan.

  Numerous approaches for the solution-based fabrication of chitosan-based materials are reported, but most often result in materials with limitations in terms of stability in aqueous systems and mechanics unless chemical cross-linking is utilized. In the present study, a thermomechanical compression method is presented for solid-state processing of chitosan powders into dense bulk plastic-like materials where the mechanical and physical properties can be tailored. To achieve this outcome, chitosan-citrate complexes, formed through ionic cross-linking and amidation, undergo thermal fusion at high temperature and pressure to generate robust materials with retention of the inherent properties of chitosan, including biodegradability and cytocompatibility. The chitosan-based plastics can be doped with enzymes and antibiotics with retention of bioactivity and are also explored as living materials when microbial cells (e.g., Pseudomonas putida) are included in the process and subsequently shown to maintain metabolic functions to degrade organic pollutants. This thermoplastic approach for solid-state processing of chitosan enables the development of a variety of new materials and composites with embedded biomolecules for enhanced functions. This solid-state fabrication of chitosan bulk materials approach eliminates the need for conventional solution-based processing, enabling rapid material production via compression molding while reducing costs, minimizing waste, and improving overall manufacturing efficiency.

Keywords:  Chitosan plastics; biodegradable; bioremediation; living materials; thermomechanical compression

DOI:  https://doi.org/10.1002/adma.202511623
ACS Mater Au. 2025 Nov 12. 5(6): 940-959

Nano- and Microscale Chemical and Topographical Patterning of Synthetic Cell Scaffolds: from Hard to Soft Materials.

Laura O Williams, Teah N Tirey, Soumya Paul, Shelley A Claridge.

  Over the past century, a growing body of work has demonstrated that cellular behavior is impacted by contact with the materials in the surrounding environment, at length scales from centimeters down to nanometers. Soft matter (such as native extracellular matrices) has historically been challenging to pattern with great precision, so early efforts to understand structured cell-material interactions in the 1990s took advantage of hard interfaces, leveraging fabrication methods developed for the electronics industry throughout the 60s and 70s. Ultimately, as it became clear that cells respond to not only topography and chemistry of their environment, but also mechanical properties, patterning methods have been extended to soft materials, although often with lower structural resolution. Here, we provide a historical overview of the development of structured cell scaffold interfaces, highlighting the potential for additional advances in material patterning translated from hard to soft matter.

Keywords:  biomaterials; cell scaffolds; extracellular matrix; hydrogels; nanomaterials; regenerative medicine; tissue engineering; tissue regeneration

DOI:  https://doi.org/10.1021/acsmaterialsau.5c00133
Nano Lett. 2025 Nov 21.

Polymer Blend Controls Nanoparticles' Surface Charge for Improved Mucus Penetration and Epithelial Cell Adhesion.

Corey A Stevens, Boris Sevarika, Brian K Wilson, Chia-Ming Wang, Gerardo Cárcamo-Oyarce, Joseph Romeo, George Degen, Timothy Kassis, Claus Michael Lehr, Rebecca L Carrier, Katharina Ribbeck, Robert K Prud'homme.

  Mucus, a viscoelastic gel composed of dense mucin glycoprotein networks, acts as a major barrier to therapeutic delivery across all epithelial surfaces by trapping nanoparticles (NPs) and preventing access to the underlying cells. To address this, we developed mucus-evading yet cell-sticky (MECS) NPs with tunable surface charge using Flash NanoPrecipitation. These 100-nanometer-diameter MECS NPs incorporate a small amount (5 wt %) of polycationic dimethylaminoethyl methacrylate (PDMAEMA) into a dense, neutral poly(ethylene glycol) (PEG) corona, which enables mucus penetration while also driving epithelial cell adhesion. In vitro cell culture and physiologically relevant gut-on-a-chip organoids demonstrate MECS NPs penetrate mucus as effectively as purely PEGylated control NPs, while exhibiting a 45-fold increase in binding to epithelial cells. This dual functionality represents a generalizable strategy for overcoming the long-standing trade-off between mucodiffusion and cellular uptake in mucosal drug delivery.

Keywords:  mucodiffusion; mucus barrier; mucus-penetrating particles; nanoparticle drug delivery; polymeric materials

DOI:  https://doi.org/10.1021/acs.nanolett.5c02487
ACS Nano. 2025 Nov 21.

Self-Assembling Protein Materials with Genetically Programmable Morphology and Size.

Jacob B Miller, Charlotte Abrahamson, Marilyn F S Lee, Brett J Palmero, Nolan Kennedy, Carolyn E Mills, Danielle Tullman-Ercek.

  Materials are challenging to synthetically program down to the atom level. Nature, however, excels at creating hierarchical materials from nanoscale building blocks, a feat that remains a major challenge in synthetic systems. A deeper understanding of the molecular rules governing self-assembly would unlock the potential for designing genetically programmable materials with atomic precision. Hexameric bacterial microcompartment (BMC-H) proteins offer a powerful model system for exploring this question. These sequence-defined proteins naturally assemble into complex architectures and can be expressed biologically, making them ideal candidates for studying how minor sequence variations influence supramolecular structure. In this work, we leverage cell-free protein synthesis (CFPS) alongside immunostaining and super-resolution microscopy to investigate the self-assembly behavior of two BMC-H proteins, PduA and PduJ. We find that both proteins form micron- to millimeter-scale structures when expressed in vitro. Further, we demonstrate how single-point mutation changes lead PduA and PduJ to form significantly different supramolecular structures when produced using CFPS. These studies support the future exploration of self-assembling proteins as programmable scaffolds in broad materials applications.

Keywords:  Bacterial Microcompartments; Biomaterials; Cell-Free Protein Synthesis; Protein Assembly; Self-Assembly; Synthetic Biology

DOI:  https://doi.org/10.1021/acsnano.5c12294
Sci Adv. 2025 Nov 21. 11(47): eadz7432

Directed self-assembly of 3D interconnected networks.

Mingchao Ma, Guillermo A Hernández-Mendoza, Baopu Zhang, Zehao Sun, Alfredo Alexander-Katz, Caroline A Ross.

Directed self-assembly (DSA) of block copolymers (BCPs) has long been included in the semiconductor roadmap as a lithographic pathway to enable continued device scaling. Tremendous progress has been made in generating two-dimensional (2D) BCP patterns with device-relevant features and low defect density and in transferring these patterns to functional materials. Extension of pattern generation into 3D could markedly enhance the utility of BCPs in nanoscale manufacturing, but methods to template and synthesize well-ordered, nontrivial 3D structures are less well developed. Here, we demonstrate a hierarchical DSA method to generate cross-point structures with connected in-plane and out-of-plane segments and controlled orientation angle between the horizontal layers. Various highly ordered, 3D interconnected networks, including ladder and cross-point structures, are produced by combinations of surface modification, BCP periodicity, and topographic templates, expanding the capabilities of BCP-derived nanofabrication.

DOI: https://doi.org/10.1126/sciadv.adz7432
ACS Macro Lett. 2025 Nov 21. 1835-1842

Biosynthetic Polyelectrolyte Composites Exhibit Tunable Scale-Dependent Mechanics Governed by Entanglements.

Farshad Safi Samghabadi, Ashlee D McGovern, Peter Edimeh, Rae M Robertson-Anderson, Jacinta C Conrad.

We engineer composites of biological DNA and synthetic sodium poly(styrenesulfonate) polymers with judiciously matched physical properties that interpenetrate to form miscible solutions spanning from semidilute to entangled regimes at varying DNA fractions wDNA and ionic strengths I. The DNA entanglement concentration robustly dictates the crossover from semidilute to entangled dynamics for all compositions and ionic strengths of composites (wDNA > 0). The effect of I emerges in the concentration dependence of viscosity, which transitions from polyelectrolyte scaling to good solvent scaling for neutral polymers as wDNA and I increase. Conversely, the dynamics at shorter spatiotemporal scales follow θ-solvent scaling. Thus, combining biological and synthetic polyelectrolytes enables independent tuning of the polyelectrolyte fingerprint, entanglement concentration, and solvent interactions, which can be leveraged for engineering miscible polymer composites with greater dynamic range and responsiveness for applications from energy storage to drug delivery.

DOI: https://doi.org/10.1021/acsmacrolett.5c00633
Nat Commun. 2025 Nov 21. 16(1): 10257

Photo-excited extracellular electron transfer of electroactive microorganism triggers RAFT polymerization.

Chao Li, Jing Liu, Wenchang Hu, Lin Xiao, Feng Li, Qijing Liu, Junqi Zhang, Huan Yu, Baocai Zhang, Dake Xu, Shaoan Cheng, Wen-Wei Li, Kenneth H Nealson, Hao Song.

Living cell-triggered reversible addition-fragmentation chain-transfer (RAFT) polymerization is of great value for construction of living materials with diverse applications. However, microorganisms-activated polymerization without end-group heterogeneity is not yet established. Here, we develop an electroactive microorganism-triggered polymerization system using Shewanella oneidensis-secreted flavins (as electron shuttles) to directly reduce chain transfer agents (CTAs) to continuously generate radicals, thus initiating RAFT polymerization. This S. oneidensis-triggered polymerization integrates microbial extracellular electron transfer pathway and photoinduced electron transfer to reduce CTAs for continuous radical generation. We then genetically engineer S. oneidensis to enhance flavins biosynthesis and transport, accomplishing increased conversion ratio ( > 90%) of poly(N, N-dimethylacrylamide) with low polydispersity (Ð < 1.20). In addition, the S. oneidensis-triggered RAFT polymerization is effective for various monomers and CTAs, being able to synthesize diverse block copolymers. Synergistic integration of synthetic biology and RAFT polymerization provides a sustainable and controllable polymerization platform.

DOI: https://doi.org/10.1038/s41467-025-65119-x
Nat Commun. 2025 Nov 20. 16(1): 10209

Spatially programmable origami networks enable high-density mechanical computing for autonomous robotics.

Xinyu Hu, Ting Tan, Yinghua Chen, Zhimiao Yan.

Mechanical computing enables logic decision-making, allowing direct computational integration into robotics to enhance their autonomy in complex environments. However, current non-universal logic designs hinder reconfigurability in multifunctional mechanical computing systems. Complexity-multifunctionality trade-offs limit mechanical computing materials to single logical operations and low computational density. Here, we address these limitations using origami metamaterials with reconfigurable conductive networks, enabling high-density programmable logic via physical reorganization. By rotating intra-gate elements to modify AND/OR-based Boolean cascades, the design reduces gates by 46.7% compared to standard arrays, executing arithmetic and comparison operations efficiently. Shared tree-like cascades allow multiple functions with minimal redundant gates. The system via Rubik's Cube mechanics supports three-axis reconfiguration of Buffer/NOT elements, achieving reconfigurable full-adder/subtractor and computational densities up to 1728. Integrated robotics demonstrate autonomous right-angled and curved path planning through reprogrammable half-adder/subtractor logic. This framework provides a universal, scalable design-methodology for high-density mechanical computing, with implications for robotics and embodied intelligence.

DOI: https://doi.org/10.1038/s41467-025-64956-0
PNAS Nexus. 2025 Nov;4(11): pgaf330

Chemical signaling in reaction networks generates corresponding mechanical impulses.

Oleg E Shklyaev, Anna C Balazs.

  Chemical reaction networks (CRNs) in the body are directed pathways that transmit reagents to reactive sites and trigger chemical processes, which ultimately instigate the appropriate physical activity. Typically, models for CRNs do not describe the coupling among chemistry, hydrodynamics and fluid-structure interactions that inherently arise in fluids. Herein, we develop a model that describes the above interrelated physicochemical behavior and show that chemical transport in a CRN spontaneously gives rise to transduction of chemistry into mechanical work, to form a complementary chemo-mechanical network (CMN). To simulate CRNs, we use the repressilator model, a reaction pathway involving biomimetic feedback loops. The encompassing material system is formed from an ordered array of enzyme-coated beads that are interlinked to form a flexible network. Coupling of chemistry and hydrodynamics occurs through the solutal buoyancy mechanism where variations in chemical concentration drive the fluid motion that deforms the flexible network of beads. Consequently, this system displays chemo-mechanical transduction as chemical signals in the CRN are converted to mechanical action. Using this model, we design materials systems encompassing CRNs that spontaneously generate CMNs, which perform the mechanical work of transporting particles or morphing the structure of the elastic network. The propagation of chemical signals along CMN that lead to mechanical actions mimic a nervous system, which transmits signals that instruct a responsive musculature.

Keywords:  biomimetic behavior; chemical reaction networks; chemo-mechanical transduction; synchronization of mobile oscillators; synthetic biology

DOI:  https://doi.org/10.1093/pnasnexus/pgaf330
bioRxiv. 2025 Sep 29. pii: 2025.09.29.678932. [Epub ahead of print]

Computational design of pH-sensitive binders.

Green Ahn, Brian Coventry, Ella Haefner, Shayan Sadre, Jenny Hu, Mimosa Van, Buwei Huang, Isaac Sappington, Adam J Broerman, Mauriz A Lichtenstein, Matthias Glögl, Inna Goreshnik, Dionne Vafeados, David Baker.

pH gradients are central to physiology, from vesicle acidification to the acidic tumor microenvironment. While therapeutics have been developed to exploit these pH changes to modulate activity across different physiological environments, current approaches for generating pH-dependent binders, such as combinatorial histidine scanning and display-based selections, are largely empirical and often labor-intensive. Here we describe two complementary principles and associated computational methods for designing pH-dependent binders: (i) introducing histidine residues adjacent to positively charged residues at binder-target interfaces to induce electrostatic repulsion and weaken binding at low pH, and (ii) introducing buried histidine-containing charged hydrogen-bonding networks in the binder core such that the protein is destabilized under acidic conditions. Using these methods, we designed binders that dissociate at acidic pH against ephrin type-A receptor 2, tumor necrosis factor receptor 2, interleukin-6, proprotein convertase subtilisin/kexin type 9, and the interleukin-2 mimic Neo2. Fusions of the designs to pH-independent binders of lysosomal trafficking receptors function as catalytic degraders, inducing target degradation at substoichiometric levels. Our methods should be broadly useful for designing pH-sensitive protein therapeutics.

DOI: https://doi.org/10.1101/2025.09.29.678932
Sci Adv. 2025 Nov 21. 11(47): eaea6883

High-strength and fracture-resistant ionogels via solvent-tailored interphase cohesion in nanofibrous composite networks.

He Zhang, Wenbin Jia, Mingze Sun, Yuxiang Chen, Xiaoyi Zhang, Hao Li, Xingdao He, Peng Shi, Lizhi Xu.

Ionogels are promising for soft robotics, energy systems, and bioelectronic interfaces due to their high ionic conductivity and environmental stability. However, combining high strength and fracture resistance remains challenging. Here, we report composite ionogels with outstanding mechanical strength (~65.4 megapascal) and fracture energy (~607 kilojoules per square meter), capable of bearing more than 5000 times their own weight. These ionogels are developed by tailoring solvent-solute interactions to create a dense, hyperconnected nanofibrous polymer network. Solvent engineering regulates hydrogen bonding competition, facilitating the formation of robust interphase hydrogen bonds and a soft-hard biomimetic interface. Moreover, their antidrying, breathable nature enables multifunctional electrophysiological monitoring, making them ideal for wearable bioelectronics. Their ionic conductivity, drug-loading capacity, and antibacterial properties allow their use in advanced e-bandages for chronic wound healing. This generalizable strategy for ionogel design opens pathways toward strong, versatile, and biocompatible materials, particularly valuable for next-generation soft materials, wearable electronics, and tissue engineering.

DOI: https://doi.org/10.1126/sciadv.aea6883
ACS Synth Biol. 2025 Nov 18.

Identification and Purification of Specific Cell Populations via ADAR Editing-Driven Synthetic Genetic Circuits.

Yu-Ting Sun, Pei-Pei Qin, Bang-Ce Ye, Bin-Cheng Yin.

  Cell separation and purification techniques are crucial in modern biomedical research and clinical applications. Endogenous RNA, which reflects a cell's genetic and physiological characteristics, provides a new way to determine cell identity at the transcriptional level. Here, we utilize RNA editing technology based on adenosine deaminase acting on RNA (ADAR) to design a dual-switch genetic circuit capable of detecting unique RNA biomarkers for cell separation and purification. The circuit incorporates a kill switch driven by barnase, which selectively eliminates nontarget cells, and a recognition switch, precisely regulated by ADAR editing, to control the expression of the MS2 bacteriophage coat protein (MCP) and barstar that inhibit barnase expression and activity. By temporally regulating these switches, our approach achieves purification efficiencies of 93-97% for HepG2, A549, and HER2-overexpressing SK-BR-3 cells in mixed populations, surpassing traditional methods. Furthermore, utilizing standard cell culture protocols, our approach simplifies cell identification and purification without interfering with the normal gene expression of target cells, ensuring robustness and safety. We believe that this ADAR-assisted genetic circuit holds great potential for applications in cell therapy and biopharmaceutical manufacturing.

Keywords:  ADAR editing; RNA biomarker; cell identification and purification; synthetic genetic circuit

DOI:  https://doi.org/10.1021/acssynbio.5c00365
Nat Commun. 2025 Nov 18. 16(1): 10040

Inverse design of structural colours in polymeric films with crystallization-induced reversible thermochromism.

Dong Yang, Heyi Liang, Chengjie Zhang, Peipei Shao, Qin Li, Yun Huang, Yi Dan, Cheng Zeng, Rui-Tao Wen, Long Jiang, Ming Xiao.

Precisely controlling structural colours in polymeric materials remains a major challenge, with current approaches often relying on trial-and-error synthesis. Here, we develop a colour design model, enabling inverse design of structural colours in bottlebrush block copolymers (BBCPs). The model can quantitatively link BBCP molecular structures to macroscopic colours through the integration of a strong segregation self-consistent field theory model with a multilayer optical framework. We first validate its predictive capability by synthesising and assembling BBCPs with varied chain architectures to produce a full colour spectrum, and then demonstrate its generalisability to other BBCP chemistries. In addition, we observe reversible, nonlinear thermochromism in systems combining a crystalisable block with a soft, low-glass transition temperature segment, while similar BBCPs lacking this pairing show no such response. Our work establishes a predictive platform for designing structurally coloured, thermoresponsive polymeric materials and advances the rational engineering of photonic soft matter.

DOI: https://doi.org/10.1038/s41467-025-66015-0
Adv Sci (Weinh). 2025 Nov 21. e13208

Multimaterial 3D Printing of Soft and Stretchable Electronics.

Omid Dadras-Toussi, Bhoomija Hariprasad, Mohammad Reza Abidian.

  The development of soft and stretchable microelectronics is critical for next-generation flexible devices, biointerfaces, and microscale energy systems due to their unique electrical and mechanical properties. However, current 3D printing methods, particularly two-photon polymerization (2PP), remain limited by low electrical conductivity, filler aggregation, and loss of optical transparency. Here, we present a multimaterial 2PP-compatible resin that integrates the conducting polymer PEDOT:PSS and multi-walled carbon nanotubes within a hydrogel PEGDA matrix to overcome these challenges. The optimized composite achieves a conductivity of 1.4 × 10⁵ S m-1 (≈10⁴-fold improvement over pristine PEGDA), > 80% optical transmittance, and stable high-resolution patterning. Directly printed microresistors and microcapacitors exhibit a specific capacitance of ≈667 F g-1, combining electric-double-layer and pseudocapacitive charge storage. The printed structures maintain ≈65% of their conductivity under 50% tensile strain and remain conductive after 3000 stretching cycles at 10% strain, with no delamination from PDMS. The composite also preserves geometry and adhesion across pH 3-10, confirming chemical robustness. This sequential multimaterial 2PP approach enables monolithic integration of conductive, insulating, and electroactive domains for flexible, stretchable, and chemically stable soft microelectronics, advancing scalable fabrication of biointerfaces, wearable devices, and microscale energy-storage systems.

Keywords:  additive manufacturing; carbon nanotubes; microelectronics; multimaterial 3D printing; two‐photon polymerization conducting polymers

DOI:  https://doi.org/10.1002/advs.202513208
J Mater Chem C Mater. 2025 Oct 28.

Electrically active hydrogels based on PEDOT:PSS for neural cultures.

Liwen Wang, Yannick Hajee, Jean-Philippe Frimat, Mani Diba, Achilleas Savva.

Electrically active hydrogels are attracting significant interest as biohybrid materials for electrical interfacing with biological tissues. Here, we report the development of electrically active hydrogels, specifically engineered for in vitro neural cell cultures. The hydrogels' matrix comprises a viscoelastic alginate primary network, interpenetrated by a secondary network formed by the neural cell-adhesive protein, laminin. Conducting poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) particles are embedded throughout the hydrogel matrix, serving as the electrically active filler phase. Oscillatory rheology confirmed the viscoelastic nature of the composite hydrogels, with storage and loss moduli in the range of 1-10 kPa, suitable for neural tissue interfacing. The hydrogels exhibited high optical transparency across the visible spectrum. At a wavelength of 500 nm, transmission exceeded 45% for 400 µm thick hydrogels and was further enhanced to over 60% by reducing the hydrogel thickness to 150 µm. We established a reproducible protocol for electrochemical impedance spectroscopy and cyclic voltammetry measurements, demonstrating that the incorporation of PEDOT:PSS significantly enhanced both conductivity and charge storage capacitance of hydrogel films. The alginate-laminin-PEDOT:PSS hydrogels demonstrated excellent operational stability, maintaining consistent electrochemical performance over 80 charging/discharging cycles and remaining structurally and functionally stable under cell culture conditions for over four weeks. Cortical neuron cultures derived from human induced pluripotent stem cells prove the stability and cytocompatibility of our proposed hydrogels for over 28 days in culture. Collectively, these results highlight the potential of electrically active hydrogels loaded with PEDOT:PSS as soft, bioelectronic interfaces for neural engineering applications.

DOI: https://doi.org/10.1039/d5tc02708j
Nat Commun. 2025 Nov 21. 16(1): 10311

Interpretable molecular decision-making with DNA-based scalable and memory-efficient tree computation.

Junlan Liu, Qian Tang, Yongqi Han, Jinxing Song, Fei Wang, Pei Guo, Chunhai Fan, Weihong Tan, Da Han.

DNA computing has emerged as a transformative paradigm for tackling computational problems at the molecular level, yet existing approaches remain constrained in algorithmic interpretability, efficiency, and scalability. Here we present a DNA-based decision tree system that modularly embeds classification rules into DNA strand displacement reaction cascades for interpretable decision-making across various configurations. It supports cascaded networks exceeding 10 layers, parallel computation of 13 decision trees in a Random Forest involving 333 strands, and multimode operation (linear/nonlinear, binary/multi-class, single/tandem trees), while maintaining low leakage, rapid signal propagation, and minimal computational elements. Coupled with a DNA-methylation sensing module, it translates biomarker profiles into molecular instructions for tree traversal, reproduces in-silico predictions and enables accurate disease subtype classification. The decision tree system represents an interpretable, scalable, and memory-efficient DNA computing approach and will open new avenues for programming intelligent molecular machines with broad applicability.

DOI: https://doi.org/10.1038/s41467-025-66610-1
ACS Appl Mater Interfaces. 2025 Nov 18.

Smart Luminescent Materials Based on Rare-Earth Complexes: From Precise Syntheses to Regulable Functions.

Nan Song, Congcong Wang, Yu Tang.

  Smart luminescent materials derived from rare-earth complexes can dynamically respond to external stimuli and exhibit a tunable emission. The performance of these materials hinges on precise control of their molecular structures. This perspective establishes a direct roadmap from precision synthesis to function regulation. We systematically discuss how ligand design, supramolecular assembly, and nanomaterial integration serve as key strategies to regulate their luminescence and unlock multifunctions. Furthermore, we critically review recent advancements in translating these smart materials into applications, such as next-generation optoelectronics, sensing, information security, and biomedicine. Finally, future challenges and opportunities in this field are outlined to guide further development.

Keywords:  intelligent; ligand design; luminescent materials; rare-earth complexes; regulation

DOI:  https://doi.org/10.1021/acsami.5c20695
Nat Mater. 2025 Nov 19.

A crystal that breathes.

DOI: https://doi.org/10.1038/s41563-025-02424-2
Mater Horiz. 2025 Nov 19.

Physics-informed neural networks for programmable origami metamaterials with controlled deployment.

Sukheon Kang, Youngkwon Kim, Jinkyu Yang, Seunghwa Ryu.

Origami-inspired structures provide unprecedented opportunities for creating lightweight, deployable systems with programmable mechanical responses. However, their design remains challenging due to complex nonlinear mechanics, multistability, and the need for precise control of deployment forces. Here, we present a physics-informed neural network (PINN) framework for both forward prediction and inverse design of conical Kresling origami (CKO) without requiring pre-collected training data. By embedding mechanical equilibrium equations directly into the learning process, the model predicts complete energy landscapes with high accuracy while minimizing non-physical artifacts. The inverse design routine specifies both target stable-state heights and separating energy barriers, enabling freeform programming of the entire energy curve. This capability is extended to hierarchical CKO assemblies, where sequential layer-by-layer deployment is achieved through programmed barrier magnitudes. Finite element simulations and experiments on physical prototypes validate the designed deployment sequences and barrier ratios, confirming the robustness of the approach. This work establishes a versatile, data-free route for programming complex mechanical energy landscapes in origami-inspired metamaterials, offering broad potential for deployable aerospace systems, morphing structures, and soft robotic actuators.

DOI: https://doi.org/10.1039/d5mh01607j
bioRxiv. 2025 Oct 02. pii: 2025.09.30.679598. [Epub ahead of print]

Generation of Cellular Biofactories for Scalable Production of Surface-Engineered Extracellular Vesicles via CRISPR Genome Editing.

Yuki Kawai-Harada, Thomas Scarborough, Nayeema Siraj, Jayadeep Yedla, Tiffany Rennells, S Patrick Walton, Christina Chan, Masako Harada.

Extracellular vesicles (EVs) are versatile biological nanoparticles with applications in therapeutics, diagnostics, and biotechnology. Current production methods using transient transfection or chemical conjugation suffer from high variability, limited scalability, and heterogeneous EV populations. Here, we developed CRISPR-Cas9 engineered HEK293T cell lines with stable integration of mCherry-C1C2 fusion proteins at the AAVS1 locus for continuous production of surface-modified EVs. The engineered cell lines demonstrated significantly higher surface display efficiency compared to transient transfection, with reduced batch-to-batch variability. EVs maintained native characteristics including size distribution (120-130 nm) and marker expression while showing efficient cellular uptake. The platform maintained consistent production of uniformly modified EVs with stable transgene expression over at least 25 passages (~3 months), eliminating the need for repeated transfections and reducing batch-to-batch variability inherent to transient expression systems.

DOI: https://doi.org/10.1101/2025.09.30.679598
Adv Mater. 2025 Nov 16. e12235

Resolving the mRNA Encapsulation-Release Trade-off via Compensatory Forces in Engineered Ionizable Lipids.

Weixiang Gao, Kang An, Yishan Ma, Xiao Xu, Ziyue Wang, Junjian Liu, Xiangfei Shan, Yuqi Liu, Wei Chen, Peicheng Wang, Changyang Zhou, Ying Ren, Xiaonan Huang, Yufei Xia.

  A critical challenge in lipid nanoparticle (LNP) delivery of messenger RNA (mRNA) is the inherent trade-off between stable encapsulation and efficient intracellular release. Here, this challenge is addressed through rationally engineering compensatory forces between mRNA and LNP, leveraging short-range intermolecular interactions (van der Waals, hydrogen bonding) to dynamically balance long-range Coulombic binding. Guided by a computational-experimental framework, a "contact number" metric is developed to decipher mRNA and LNP binding hierarchies, enabling the strategic incorporation of short-range-interaction motifs (e.g., urea, carbamate) into ionizable lipid (IL) structures. These designs achieve optimal mRNA encapsulation while promoting endosomal escape and cytosolic release, resulting in enhanced mRNA translation. Compared to commercial mRNA vaccine counterparts, the engineered LNP (OT13-LNP) induces a 1.7-fold increase in antigen-specific T cell responses and 77.9% tumor inhibition in melanoma. In hepatic gene editing, OT13-LNPs achieve comparable transthyretin (TTR) on-target editing efficiency to ALC0315-LNPs (0.5 mg kg-1), but elicit a markedly stronger silencing effect, reducing serum TTR levels by over 90% compared with ≈58% for ALC0315-LNPs. This study may highlights the potential of compensatory-force engineering for next-generation mRNA therapeutics in oncology, gene editing, and infectious diseases.

Keywords:  compensatory force; gene editing; lipid nanoparticle; mRNA vaccine; short‐range interaction

DOI:  https://doi.org/10.1002/adma.202512235
Angew Chem Int Ed Engl. 2025 Nov 17. e20677

Frame-Shifted Synthesis of Oligoheterocycles as a Platform for Molecular Design.

Kane A C Bastick, Caleb E Griesbach, Ben Zhen Huang, Morgan J Cordell, Yang Daniel Ou, Alán Aspuru-Guzik, Andrei K Yudin.

  Chemists continue to develop strategies that leverage abundant feedstocks to accelerate the production of medicines, agrochemicals, and materials. Oligoheterocycles are a broad class of molecules that span these disciplines. Cross-coupling strategies are commonly used to assemble oligoheterocycles; however, these methods can be challenging and often rely on precious metal catalysts and building blocks whose production entails significant environmental and economic costs. We present a strategy for the iterative construction of oligoheterocycles that leverages sustainable building blocks designed around high-oxidation-state carbon. By utilizing feedstocks from the base of the chemical supply chain, we generate bifunctional building blocks that chemoselectively engage with a variety of partners through simple condensation manifolds. This approach has enabled the creation of novel scaffolds previously inaccessible by conventional means, exemplifying sustainable design strategies.

Keywords:  Cross‐condensation; Frame‐shifted synthesis; Heterocycles; Synthesis design; Synthetic methods

DOI:  https://doi.org/10.1002/anie.202520677
Biotechnol Adv. 2025 Nov 17. pii: S0734-9750(25)00247-2. [Epub ahead of print] 108761

Capitalizing on mechanistic insights to power design of future-ready intracellular optogenetics tools.

Si Bin Chew, Emily Harjabrata, Cameron Jing Han Goh, Qunxiang Ong.

  Intracellular optogenetics represents a rapidly advancing biotechnology that enables precise, reversible control of protein activity, signaling dynamics, and cellular behaviours using genetically encoded, light-responsive systems. Originally pioneered in neuroscience through channelrhodopsins to manipulate neuronal excitability, the field has since expanded into diverse intracellular applications with broad implications for medicine, agriculture, and biomanufacturing. Key to these advances are photoreceptors such as cryptochrome 2 (CRY2), light-oxygen-voltage (LOV) domains, and phytochromes, which undergo conformational changes upon illumination to trigger conditional protein-protein interactions, localization shifts, or phase transitions. Recent engineering breakthroughs-including the creation of red-light responsive systems such as MagRed that exploit endogenous biliverdin-have enhanced tissue penetration, minimized phototoxicity, and expanded applicability to complex biological systems. This review provides an overarching synthesis of the molecular principles underlying intracellular optogenetic actuators, including the photophysical basis of light-induced conformational changes, oligomerization, and signaling control. We highlight strategies that employ domain fusions, rational mutagenesis, and synthetic circuits to extend their utility across biological and industrial contexts. We also critically assess current limitations, such as chromophore dependence, light delivery challenges, and safety considerations, so as to frame realistic paths towards translation. Looking ahead, future opportunities include multi-colour and multiplexed systems, integration with high-throughput omics and artificial intelligence, and development of non-invasive modalities suited for in vivo and industrial applications. Intracellular optogenetics is thus emerging as a versatile platform technology, with the potential to reshape how we interrogate biology and engineer cells for therapeutic, agricultural, and environmental solutions.

Keywords:  Artificial intelligence; Cryptochromes; Future-ready applications; Intracellular optogenetics; LOV domains; Phytochromes

DOI:  https://doi.org/10.1016/j.biotechadv.2025.108761
Small. 2025 Nov 18. e09316

Orchestrating Self-Replication in Artificial Cells with Digital Microfluidics.

Guanzhong Zhai, Pantelitsa Dimitriou, Jason Sengel, Mark Ian Wallace.

  A defining feature of living cells is their ability to self-replicate; but creating artificial cells with this capability remains challenging, due to the complexity of biological division machinery. Rather than seeking to reconstitute this machinery, direct control of DNA replication and compartment division using digital microfluidics (DMF). This approach allows us to precisely orchestrate these two fundamental processes, providing insight into how they must be coupled for successful self-replication. The system achieves controlled cycles of replication and division, with daughter compartments inheriting parental DNA and maintaining genetic continuity across multiple generations - a key feature of living systems that has been difficult to achieve in artificial cells. By implementing these processes through direct physical manipulation rather than biochemical complexity, a simple testbed is provided that will help to disentangle the essential requirements for self-replicating systems.

Keywords:  artificial cells; digital microfluidics; self‐replication

DOI:  https://doi.org/10.1002/smll.202509316
Acc Chem Res. 2025 Nov 21.

A Versatile Platform for Recyclable Polyesters: Alternating Copolymerization of Aldehydes (or Their Derivatives) with Cyclic Anhydrides.

Xun Zhang, Chengjian Zhang, Xinghong Zhang.

ConspectusThe rapid expansion of the global polymer industry has highlighted the urgent need for sustainable alternatives to traditional synthetic polymers, which are predominantly derived from nonrenewable fossil resources and pose significant environmental challenges due to their persistence in ecosystems. In response, the development of chemically recyclable polymers has emerged as a promising strategy to reconcile the utility of polymer materials with the imperative of sustainability. However, the synthesis of such polymers often faces limitations in monomer diversity, polymerization efficiency, and the ability to achieve true chemical recyclability.In this Account, we present a comprehensive overview of our recent advancements in the synthesis of chemically recyclable polyesters through the alternating copolymerization of aldehydes (or their derivatives) with cyclic anhydrides. This approach leverages abundant and cost-effective feedstocks, including aldehydes derived from renewable resources and cyclic anhydrides prepared from biorenewable diacids, to create a versatile platform for sustainable polymer synthesis. By employing a wide range of monomers, we have successfully synthesized over 140 polyesters with highly tunable structures and properties.A key feature of this copolymerization is its chemical reversibility, a thermodynamic characteristic arising from a low reaction enthalpy change. This results in a ceiling temperature behavior, wherein the polymer becomes unstable with respect to its monomers upon heating. This chemical reversibility is the fundamental principle that enables the efficient, closed-loop chemical recycling that we demonstrate. Additionally, the water-degradable properties of certain copolymers, particularly those derived from formaldehyde, offer a pathway for developing polymers that can fully degrade into valuable small molecules in water or seawater. This feature is particularly significant in the context of marine pollution, where traditional plastics persist for centuries. Furthermore, the polyesters derived from Schiff bases exhibited unique self- and autodegradation properties. This tunable degradation behavior, governed by polymer structure, provides a versatile tool for designing materials with tailored life spans. Moreover, the mechanical and flame-retardant properties of polyesters derived from chloral and cyclic anhydrides make them promising alternatives to conventional poly(vinyl chloride).The broader implications of these studies extend beyond the synthesis of sustainable polyesters. By demonstrating the feasibility of utilizing renewable resources for polymer production, we contribute to the development of a circular economy, where materials are designed with their end-of-life considerations in mind. Future research will focus on expanding the scope of monomers, optimizing polymerization conditions, and integrating these materials into industrial processes.

DOI: https://doi.org/10.1021/acs.accounts.5c00645
Nat Commun. 2025 Nov 20. 16(1): 10221

G4mer: An RNA language model for transcriptome-wide identification of G-quadruplexes and disease variants from population-scale genetic data.

Farica Zhuang, Danielle Gutman, Nathaniel Islas, Bryan B Guzman, Alli Jimenez, San Jewell, Nicholas J Hand, Katherine Nathanson, Daniel Dominguez, Yoseph Barash.

RNA G-quadruplexes (rG4s) are key regulatory elements in gene expression, yet the effects of genetic variants on rG4 formation remain underexplored. Here, we introduce G4mer, an RNA language model that predicts rG4 formation, classifies rG4 subtypes, and evaluates the effects of genetic variants across the transcriptome. G4mer significantly improves accuracy over existing methods and uncovers subtype-specific differences in mutational sensitivity and evolutionary constraint, highlighting sequence length and flanking motifs as important rG4 features. Applying G4mer to 5' untranslated region (UTR) variations, we identify variants in breast cancer-associated genes that alter rG4 formation and validate their impact on structure and gene expression. These results demonstrate the potential of integrating computational models with experimental approaches to study rG4 function, especially in diseases where non-coding variants are often overlooked. To support broader applications, G4mer is available as both a web tool and a downloadable model.

DOI: https://doi.org/10.1038/s41467-025-65020-7
Science. 2025 Nov 20. 390(6775): 824-830

Increasing the dimensionality of transistors with hydrogels.

Dingyao Liu, Jing Bai, Xinyu Tian, Yan Wang, Binbin Cui, Shilei Dai, Wensheng Lin, Zhuowen Shen, Chun Kit Lai, George G Malliaras, Shiming Zhang.

Transistors, fundamental to modern electronics, are traditionally rigid, planar, and two-dimensional (2D), limiting their integration with the soft, irregular, and three-dimensional (3D) nature of biological systems. Here, we report 3D semiconductors, integrating organic electronics, soft matter, and electrochemistry. These 3D semiconductors, in the form of hydrogels, realize millimeter-scale modulation thickness while achieving tissue-like softness and biocompatibility. This breakthrough in modulation thickness is enabled by a templated double-network hydrogel system, where a secondary porous hydrogel guides the 3D assembly of a primary redox-active conducting hydrogel. We demonstrate that these 3D semiconductors enable the exclusive fabrication of 3D spatially interpenetrated transistors that mimic real neuronal connections. This work bridges the gap between 2D electronics and 3D living systems, paving the way for advanced bioelectronics systems such as biohybrid sensing and neuromorphic computing.

DOI: https://doi.org/10.1126/science.adx4514
Small. 2025 Nov 21. e09320

Nature-Inspired Janus Actuators with Structurally Engineered PEDOT:PSS.

Hatef Yousefian, Ali Akbar Isari, Amin Babaei-Ghazvini, Bishnu Acharya, Ahmadreza Ghaffarkhah, Mohammad Arjmand.

  Inspired by natural systems such as pinecones and seedpods, bilayer actuators enable programmable shape transformations through differential responses to external stimuli, making them promising for soft robotics and adaptive devices. However, issues such as interfacial delamination, high driving voltages, and excessive heat generation hinder their practical use. Here, a facile strategy is developed to fabricate a high-performance poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) Janus actuator capable of large, reversible bending deformation in response to electrical current, heat, humidity, and organic vapor. The actuator features a seamless interface between a conductive, hydrophobic-treated layer and a semiconductive, hydrophilic untreated layer, effectively eliminating delamination common in bilayer structures. This structural engineering is enabled by a novel "dual treatment" approach that combines solvent doping and acid post-treatment, producing a substantial conductivity contrast (≈2000 S cm-1) between the two sides while preserving structural integrity. The resulting actuator exhibits excellent electro-thermo-mechanical performance, achieving reversible curvature values of 2.4 to 3.4 cm-1 at low operating voltages (2 to 6 V) with minimal surface heating (≈5 °C). It also demonstrates outstanding durability over 2,400 actuation cycles. This work introduces a scalable and energy-efficient design platform for next-generation soft actuators, bio-inspired adaptive materials, and intelligent sensing systems.

Keywords:  PEDOT:PSS Janus film; bilayer soft actuator; dual treatment; electrical conductivity; hydrophobicity

DOI:  https://doi.org/10.1002/smll.202509320
Adv Mater. 2025 Nov 18. e16185

Autonomous Spatiotemporal Regulation of Reversible Hydrogel Actuators by Chemical Reaction Networks.

Fan Liao, Ajith George, Xiao-Meng Sui, Sergey N Semenov.

  Achieving autonomous spatiotemporal regulation of reversible hydrogel movement remains challenging, as existing approaches typically rely on external regulation or irreversible actuation mechanisms. This work presents the autonomous spatiotemporal regulation of reversible hydrogel actuators using thiol-based chemical reaction networks (CRNs). The core innovation is a bilayer actuator whose active layer is functionalized with phenylcyanoacrylate Michael acceptors. In their initial state, these groups are hydrophobic, keeping the active layer moderately collapsed. Binding to thiols, such as cysteamine or thiocholine, converts the acceptors into more hydrophilic adducts. This change drives water uptake, causing the active layer to swell and the entire structure to bend. The screening revealed that a methoxy-substituted acceptor provides the optimal balance of binding strength and reversibility for robust actuation. Autonomous control of reversible actuation is achieved by an autocatalytic, thiol-producing CRN coupled with negative feedback in the form of slow oxidation of thiols or their irreversible addition to acrylamides. In the hydrogel, this CRN generates a wave of thiols, which causes forward and reverse actuation. This principle is demonstrated with linear, flower-shaped, and hand-like actuators. This integrated system, which unites reversible chemistry with spatiotemporal control, takes a significant step toward emulating the autonomy of motion found in living systems.

Keywords:  actuators; autocatalysis; chemical reaction networks; hydrogels; thiols

DOI:  https://doi.org/10.1002/adma.202516185
Nat Commun. 2025 Nov 20.

Light-mediated communication in responsive materials ranging from individual self-oscillators to feedback-driven network.

Hongshuang Guo, Kai Li, Jianfeng Yang, Dengfeng Li, Fan Liu, Hao Zeng.

The natural interactive materials under far-from-equilibrium conditions have significantly inspired advances in synthetic biomimetic materials. In artificial systems, there are means of interaction between individuals, for instance, mechanical contact, hydrodynamic coupling, thermal gradient, chemical diffusion and magnetic field. However, they generally lack high directionality or sufficient interaction ranges. Here, we present a method for constructing highly directed, interactive structures via optical feedback in light responsive materials far from their thermodynamic equilibria. We showcase a photomechanical operator system comprising a baffle and a soft actuator. Positive and negative operators are configured to induce light-triggered deformations, alternately interrupting the passage of two light beams in a closed feedback loop. The fundamental functionalities of this optically interconnected material loop include homeostasis-like self-oscillation and signal transmission from one material to another via light. Refinements in optical alignment allow remote sensing and feedback networks capable of adaptation in both materials' shape-morphing states and oscillating frequencies. The results show a versatile design method for light-mediated interaction among responsive materials, with applicability in everyday materials.

DOI: https://doi.org/10.1038/s41467-025-66395-3
Methods Enzymol. 2025 ;pii: S0076-6879(25)00387-8. [Epub ahead of print]723 299-426

The open-source Masala software suite: Facilitating rapid methods development for synthetic heteropolymer design.

Tristan Zaborniak, Noora Azadvari, Qiyao Zhu, S M Bargeen A Turzo, Parisa Hosseinzadeh, P Douglas Renfrew, Vikram Khipple Mulligan.

  Although canonical protein design has benefited from machine learning methods trained on databases of protein sequences and structures, synthetic heteropolymer design still relies heavily on physics-based methods. The Rosetta software, which provides diverse physics-based methods for designing sequences, exploring conformations, docking molecules, and performing analysis, has proven invaluable to this field. Nevertheless, Rosetta's aging architecture, monolithic structure, non-open source code, and steep development learning curve are beginning to hinder new methods development. Here, we introduce the Masala software suite, a free, open-source set of C++ libraries intended to extend Rosetta and other software, and ultimately to be a successor to Rosetta. Masala is structured for modern computing hardware, and its build system automates the creation of application programming interface (API) layers, permitting Masala's use as an extension library for existing software, including Rosetta. Masala features modular architecture in which it is easy for novice developers to add new plugin modules, which can be independently compiled and loaded at runtime, extending functionality of software linking Masala without source code alteration. Here, we describe implementation of Masala modules that accelerate protein and synthetic peptide design. We describe the implementation of Masala real-valued local optimizers and cost function network optimizers that can be used as drop-in replacements for Rosetta's minimizer and packer when designing heteropolymers. We explore design-centric guidance terms for promoting desirable features, such as hydrogen bond networks, or discouraging undesirable features, such as unsatisfied buried hydrogen bond donors and acceptors, which we have re-implemented far more efficiently in Masala, providing up to two orders of magnitude of speedup in benchmarks. Finally, we discuss development goals for future versions of Masala.

Keywords:  Rosetta; computational peptide design; macromolecular modelling; optimization; software; structure prediction

DOI:  https://doi.org/10.1016/bs.mie.2025.09.015
bioRxiv. 2025 Oct 02. pii: 2025.10.02.680069. [Epub ahead of print]

Sequence-encoded interactions program internal condensate architecture.

Sumit Majumder, Ashif Akram, Angelina Ning, Jeremy Schmit, Ankur Jain.

Many cellular condensates, such as the nucleolus and stress granules, contain multiple coexisting phases with distinct compositions and material properties. This internal organization is crucial for function, yet how it is established remains unclear. Here, using a programmable DNA system, we reveal how molecular interactions can precisely encode multiphase architecture. We find that phase separation drives macromolecules into a semi-dilute regime where subtle differences in homotypic interaction energies are amplified into dominant organizational forces. A critical interaction energy threshold must be overcome to trigger internal demixing, after which molecular partitioning scales near-linearly with interaction strength. This universal relationship is captured by an associative polymer model, and enables engineering of condensates with up to four coexisting phases exhibiting 100-fold differences in viscosity within the same droplet. These design principles extend to RNA-peptide systems, establishing a general framework for how sequence can program hierarchical self-assembly and organize biological matter.

DOI: https://doi.org/10.1101/2025.10.02.680069