bims-enlima 2026-07-26 papers

bims-enlima

Biomed News

on Engineered living materials

Issue of 2026–07–26
27 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool

Chemical actuation expands the design space of living light materials.
Boolean Logic-Based Control Over Recombinant Protein Biomaterial Degradability and Therapeutic Delivery.
A programmable fungal platform for engineered living textiles.
Gene Editing-Driven Engineering of Microbial Systems and Metabolites for Precision Medicine and Sustainable Environmental Remediation.
Geomimicry: Emergent dynamics in Earth-mediated complex materials.
Programable and Spatially Conforming Assembly of Engineered Living Materials Onto Electrodes via Redox.
Programmable DNA-Based Dimerization Networks for Dynamic and Competitive Control of Transcription.
Charged agar surfaces affect E. coli biofilm properties, inducing a trade-off between curli amyloid quantity and quality.
Temporal morphing of hydrogels with patterned cream as a sacrificial mask for controlled diffusion and swelling.
High-Strength, Self-Sensing Multiphase Hydrogels for Load-Bearing Actuation and Logical Human-Machine Interaction.
Acoustic Tweezers-Assisted Biomaterial Molding in Petri Dishes (TAMP) for Engineering Glioma Tissues With Controlled Cellular and Extracellular Matrix Architectures.
AI-redesigned starting points and outcomes enhance protein evolution.
Engineering microbial consortia for distributed signal processing.
Neuromorphic tissues: Soft biomolecular networks for brain-inspired temporal computing.
Chemically Responsive Protein Switches for the Precise Control of Biological Activities.
DNA-FLASH─a DNAzyme Walker-Based Nanosensor for Digital Biosensing at the Point of Care.
Bioengineering toughened, stretchable bacterial cellulose-based films inspired by spider silk.
Redefining 3D cell culture: Human methacryloyl platelet lysates hydrogels for reliable, consistent, and ethical applications.
Highly Entangled Bottlebrush Polymer Networks.
Model-Assisted Prioritization of Gelatin Methacryloyl (GelMA) Hydrogel Formulations for Three-Dimensional Cell Culture.
Why shear adhesion is not monotonically enhanced by stiffening.
Mechanostereochemical modulation of polymer mechanical properties.
Engineering a Gluconate Bypass Carbon Entry Architecture for Robust Stationary Phase Biomanufacturing.
Geometry-Encoded Programmable Mechanics in Single-Material Dual-Phase Metamaterials.
Photoactivable Surfactant Design for In Situ Stabilization of Hydrogel Bioelectronics.
Development and characterization of LipoCatch: a bacterial lipoprotein-based biomaterial that self-assembles into nanostructures.
Water Droplet Hammer: Piezoelectric Sensing of Ultrafast Mechanical Transients During Droplet Impact.

Trends Biotechnol. 2026 Jul 21. pii: S0167-7799(26)00287-8. [Epub ahead of print]

Chemical actuation expands the design space of living light materials.

Anna M Duraj-Thatte.

  Chemical stimulation represents a new strategy for controlling bioluminescence in engineered living materials (ELMs). Brachi et al. demonstrate that embedding the naturally bioluminescent dinoflagellate Pyrocystis lunula within 3D-printed hydrogels enables sustained, reusable optical responses through chemical and mechanical activation. This work expands the design strategies available for optically ELMs.

Keywords:  Pyrocystis lunula; bioluminescence; chemical stimulation; engineered living materials; stimuli-responsive materials

DOI:  https://doi.org/10.1016/j.tibtech.2026.07.008
Adv Mater. 2026 Jul 21. e74038

Boolean Logic-Based Control Over Recombinant Protein Biomaterial Degradability and Therapeutic Delivery.

Murial L Ross, Ryan Gharios, Shivani Kottantharayil, Cole A DeForest.

  Recombinant protein-based biomaterials offer exciting opportunities in materials design and controlled therapeutic delivery. Though their precursors can be readily synthesized with near-perfect monodispersity and sequence specificity through scalable fermentation processes, recombinant protein materials have yet to achieve the same level of multi-stimuli-responsiveness as their synthetic counterparts. Integrating cutting-edge tools from chemical biology, we autonomously compile topologically specified protein crosslinkers that can be degraded following user-programmable Boolean logic. Covalent step polymerization of these linkers into protein hydrogels yields smart materials whose cargo (e.g., bioactive proteins, cellular therapeutics) can be liberated following bulk degradation in response to user-specified input combinations. Demonstrating the versatility of this approach, we release fluorescent protein mGreenLantern following all 17 possible YES/OR/AND logic outputs in response to a 3-input protease operator set, deliver epidermal growth factor following advanced biocomputation while maintaining native bioactivity, and showcase multiplexed delivery of living cells, all from fully recombinant protein-based hydrogels. Incorporating advanced intelligence into protein biomaterial responsiveness, we anticipate these methods will dramatically expand potential applications in tissue engineering and precision medicine.

Keywords:  biomaterials; boolean logic; controlled release; drugamer; recombinant proteins; stimuli‐responsive

DOI:  https://doi.org/10.1002/adma.74038
Sci Adv. 2026 Jul 24. 12(30): eaed6937

A programmable fungal platform for engineered living textiles.

Ke Li, Bolin An, Jicong Zhang, Dongmin Xun, Xinyi Yuan, Youyang Song, Xinyu Wang, Chao Zhong.

A central challenge in engineered living materials (ELMs) is the seamless integration of macroscopic structural assembly with sustained cellular viability and programmable function. Here, we report a fungal-based living material that addresses this challenge by preserving the metabolic activity of Cordyceps militaris mycelia within macroscale, cohesive films fabricated via a low-energy process. These living textiles retain the capacity for environmental response, demonstrated by nutrient-induced aerial hyphal growth that enables surface renewal. The native mycelial architecture further allows for volumetric integration of engineered microbial partners, exemplified by coculture with pigment-producing Saccharomyces cerevisiae for in situ patterning and melanized Aspergillus niger for built-in ultraviolet shielding. This modular design decouples bulk structural fabrication from genetic functionalization, offering a plug-and-play platform for synthetic biology. Environmental assessments confirm near-complete morphological degradation within 41 days. Our work establishes a scalable and sustainable chassis for functional ELMs, bridging a critical gap between structural integrity and biological programmability.

DOI: https://doi.org/10.1126/sciadv.aed6937
Small. 2026 Jul 21. e74410

Gene Editing-Driven Engineering of Microbial Systems and Metabolites for Precision Medicine and Sustainable Environmental Remediation.

Yangyang Du, Yunjia Shi, Dazhi Chen, Shuang Wang, Juanjuan Su, Kai Liu, Hongjie Zhang, Fan Wang.

  The engineering of microorganisms is undergoing a fundamental paradigm shift, transitioning from the construction of static cell factories to the programming of dynamically responsive living materials. However, translating molecular interventions into robust macroscopic functions requires overcoming distinct microbial-specific barriers, including delivery bottlenecks and genetic stability. In this review, we establish a unified Edit-Reprogram-Functionalize conceptual framework that systematically delineates transient genetic regulation from permanent genomic engineering. We critically examine the evolutionary trajectories of five foundational technologies: plasmid engineering, CRISPR-Cas systems, base editors, prime editors, and enzyme engineering. Rather than analyzing these toolsets in isolation, we map their convergence into an integrated engineering continuum that drives the precise synthesis of two distinct output classes: engineered living microbial materials and robust microbial metabolite-derived materials. By evaluating representative breakthroughs-from ultrasound-actuated bacterial therapeutics to ultra-tough, biosynthesized protein composites-through the strict lens of host-dependent constraints, we reveal the mechanistic principles governing successful preclinical translation. Finally, we propose an actionable roadmap centered on systemic miniaturization, closed-loop control, and multi-scale integration, providing a definitive blueprint for the next generation of precision medicine, advanced biomanufacturing, and ecological remediation.

Keywords:  biomanufacturing; enzyme engineering; gene editing; microbial engineering; precision medicine

DOI:  https://doi.org/10.1002/smll.74410
Phys Rev E. 2026 Jun;113(6-1): 061002

Geomimicry: Emergent dynamics in Earth-mediated complex materials.

Shravan Pradeep, Emanuela Del Gado, Douglas J Jerolmack, Paulo E Arratia.

Soils and sediments are soft, amorphous materials with complex microstructures and mechanical properties. They are also building blocks for industrial materials such as concrete. These Earth-mediated materials evolve under prolonged environmental pressures such as mechanical stress, chemical gradients, and biological activity. Here, we introduce geomimicry, a new paradigm for designing sustainable materials by learning from the emergent and adaptive dynamics of Earth-mediated matter. Drawing a parallel to biomimicry, we posit that these geomaterials follow evolutionary design rules, adapting their structure and function in response to persistent natural forces through locally evolved interactions and compositions. Our central argument is that by decoding these rules-primarily through understanding the emergence of novel exotic properties from multiscale interactions between heterogenous components-we can engineer a new class of adaptive, sustainable matter. We propose two complementary approaches here. The top-down approach looks to nature to identify building blocks and map them to functional groups defined by their mechanical (rather than chemical) behaviors, and then examine how environmental training tunes interactions among these groups. The bottom-up approach seeks to leverage and test this framework, building earth materials one component at a time under fluctuating environmental stresses that guide assembly of complex and out-of-equilibrium materials. The goal is to create materials with programed functionalities, such as erosion resistance or self-healing capabilities. Geomimicry offers a pathway to truly design Earth-mediated circular materials, with potential applications ranging from climate-resilient soils and smart agriculture to new insights into planetary terraforming, fundamentally shifting the focus from static compositions to dynamic, evolving systems that are mediated via their environment.

DOI: https://doi.org/10.1103/fcwk-wl2s
Small Sci. 2026 Jul;6(7): e70331

Programable and Spatially Conforming Assembly of Engineered Living Materials Onto Electrodes via Redox.

Chen-Yu Chen, Monica J Chu, Fauziah Rahma Zakaria, Eunkyoung Kim, Divya Muthusamy, Gregory F Payne, William E Bentley.

  We developed an electrobiofabrication methodology that assembles well-defined cell/gel formations directly onto electrodes. For this, we oxidatively crosslinked terminal thiols of a 4-arm thiolated polyethylene glycol (PEG) by the purposeful addition of a ferrocene redox mediator to a PEG/cell assembly solution and the application of an oxidizing charge to an electrode. Because the resulting disulfide bonds are created near the electrode, the crosslinked hydrogel assembly is defined by the electrode dimensions and the time over which the oxidative potential is applied. Results indicate a strong positive correlation between the mediator concentration, the delivered oxidative charge, the number density of cells in the assembly solution and the subsequent gel thickness and density. In all cases tested, the viability of the assembled cells (E. coli bacteria) was near 100%. We further demonstrated a gravity-mediated layering methodology to create spatially defined interfaces, as well as electroassembly onto various conductive materials of nearly arbitrary shape. These results represent a means for electronic or "programed" assembly of cell laden hydrogels, enabling further study of cell-cell interactions, cell-device interactions, biosensing, device ⇔ bio communication, and several applications such as electrogenetics wherein cell genetic circuits are actuated by application of electrical potentials using a redox-enabled communication modality.

Keywords:  bioelectronics; electrobiofabrication; electrochemical sensing; hydrogel

DOI:  https://doi.org/10.1002/smsc.70331
J Am Chem Soc. 2026 Jul 20.

Programmable DNA-Based Dimerization Networks for Dynamic and Competitive Control of Transcription.

Miriam Quattrociocchi, Simone Brannetti, Erica Del Grosso, Francesco Ricci.

Here, we introduce a minimal, experimentally validated DNA-encoded analogue of many-to-many protein dimerization networks to achieve programmable control of cell-free transcription. To do so, we rationally designed DNA monomers bearing orthogonal azide or DBCO handles that assemble via SPAAC chemistry into a combinatorial library of covalent dimers where only a single dimer completes an otherwise inactive promoter and activates transcription of a light-up RNA aptamer. By expanding the network from 2 to 22 monomers, we show that the RNA yield can be finely tuned over more than an order of magnitude, in quantitative agreement with a simple combinatorial model in which the activator dimer fraction decreases as a function of network size. We also designed sequence-defined inputs that selectively sequester monomers to reduce network size and upregulate chosen dimer activators, enabling multiplexed, orthogonal activation of different templates in the same solution from a shared monomer pool. Coupling the dimerization layer to a CRISPR-Cas12a collateral cleavage module, we further show that competitive DNA dimerization transcription logic can be interfaced with downstream enzymatic reactions to convert input sets into amplified cleavage activity. Together, these results establish competitive covalent DNA dimerization networks as a modular and quantitatively predictable platform for implementing competitive many-to-many dimerization logic for controlling cell-free transcription outputs.

DOI: https://doi.org/10.1021/jacs.6c02173
Biofilm. 2026 Dec;12 100382

Charged agar surfaces affect E. coli biofilm properties, inducing a trade-off between curli amyloid quantity and quality.

Macarena Siri, Mónica Vázquez-Dávila, Cécile M Bidan.

  Biofilm extracellular matrix (ECM) varies with environmental conditions and substrate properties. Understanding the surface-biofilm relationship helps to perfect antibacterial strategies and to design new engineered living materials (ELMs). In this work, we studied how cationic and anionic polyelectrolyte coatings affect macroscopic features of Escherichia coli curli-producing biofilms, as well as the properties of their curli amyloid fibers. Cationic coatings limited biofilm spreading, increased their surface density and water absorption, which correlated with a higher yield of curli amyloid fibers with looser structure. In contrast, anionic surfaces allowed for standard biofilm spreading, with a lower fiber yield but a more compact and chemically stable fiber structure. Higher biofilm rigidity and adhesion were measured on both types of charged surfaces. Thus, we propose that the differences in biofilm macroscopic properties result from a trade-off between curli quantity and quality in the ECM, namely fiber density and molecular packing, as well as their interaction with water. Our findings provide insights on how the biophysical properties of the ECM can be controlled by tuning the substrate physico-chemical characteristics with charged coatings. This work opens up new avenues for developing antimicrobial strategies, as well as tailoring the properties of amyloid-based ELMs.

Keywords:  Bacterial matrix; Biofilm mechanics; Fiber structure; Polyelectrolyte coating; Water uptake

DOI:  https://doi.org/10.1016/j.bioflm.2026.100382
Mater Horiz. 2026 Jul 21.

Temporal morphing of hydrogels with patterned cream as a sacrificial mask for controlled diffusion and swelling.

Xin Ling Wen, Xing Peng Hao, Hao Xue Du, Zhi Jian Wang, Yilan Ye, Zi Liang Wu.

Materials capable of undergoing controllable, transient deformations to perform temporary functions and subsequently recover their original shapes are of great interest for soft devices and adaptive systems. In hydrogels, such temporal morphing can be achieved by spatiotemporally regulating the transport of water or chemical stimuli. Here, we report a straightforward and adaptable strategy using a soluble pseudoplastic hand cream as a sacrificial mask to pattern the gel surface and enable asymmetric diffusion and thus controllable temporal morphing. The cream locally inhibits water diffusion, creating a transient swelling gradient that induces programmed, temporary deformations. As the cream dissolves and water diffusion gradually equilibrates, the hydrogel recovers its final equilibrium shape. The dynamics and intermediate configurations of the transient deformation are governed by the kinetics of water diffusion within the hydrogel, which is regulated by the spatial distribution and dissolution kinetics of the cream masking layer. The pseudoplastic nature of the cream allows easy patterning into diverse spatial distributions with tunable thickness, enabling complex shape transformations with tunable deformation and recovery dynamics. This sacrificial-mask-based temporal morphing strategy is applicable to various hydrogel materials. We further demonstrate the utility of this temporal morphing strategy in representative scenarios, including object transport through confined spaces and light signal control, highlighting its potential for time-dependent shape-morphing regulated functions.

DOI: https://doi.org/10.1039/d6mh00791k
Nanomicro Lett. 2026 Jul 23. pii: 450. [Epub ahead of print]18(1):

High-Strength, Self-Sensing Multiphase Hydrogels for Load-Bearing Actuation and Logical Human-Machine Interaction.

Zhilin Zhang, Jiayi Gu, Lina Wang, Xingchen Cui, Xu Zhai, Yue Xu, He Liu, Deliang Li, Bingle Li, Ye Tian, Baoyang Lu, Yu Fu, Tieqiang Wang.

  Stimuli-responsive shape-changing hydrogels are the most competitive candidates for artificial muscles, electronic skins, and soft robotics. However, existing actuating hydrogels often suffer a trade-off between actuation performance and mechanical strength, which greatly limits their application prospects as actuators under external force loads. Here, we adopt a cascade polymerization strategy to successively introduce electrical sensing and mechanically enhanced polymer network phases into sponge-like PNIPAM hydrogels to achieve PNIPAM-based photothermal-responsive actuating hydrogels with fast response, high strength, and self-sensing performance. The as-prepared hydrogel actuator can execute rapid actuation missions even under external loading far exceeding its own mass and generate differentiated electrical sensing signals according to the magnitude of the external load. Based on the corresponding relationship between the mass of the load and the actuation behavior (such as "0/1" encoding), we develop a novel material-based binary information encoding system. Furthermore, by manufacturing logic gates to analyze differentiated feedback sensing signals and integrating them with Internet of Things technology, a closed-loop logic control system is established for remote logic-based interactive communication. This study fills the gap of traditional hydrogels in load-bearing actuation and complex interactive applications and opens up a new direction for the next generation of smart soft materials.

Keywords:  Actuator; High-strength; Human–machine interaction; Information encoding system; Multicontinuous-interpenetrating network

DOI:  https://doi.org/10.1007/s40820-026-02280-y
Small. 2026 Jul 19. e74599

Acoustic Tweezers-Assisted Biomaterial Molding in Petri Dishes (TAMP) for Engineering Glioma Tissues With Controlled Cellular and Extracellular Matrix Architectures.

Yingshan Du, Jiali Li, Hui Liu, Julio P Arroyo, Luyu Bo, Bowen Cai, Teng Li, Zhide Wang, Chongpeng Qiu, Rafael Davalos, Joseph Rich, Zhenhua Tian.

  Tissue engineering has shown great potential for manufacturing tissue replacements and developing physiologically relevant tissue models. However, conventional tissue engineering strategies often face challenges in fabricating tissues simultaneously incorporating controlled cellular and extracellular matrix (ECM) architectures. Here, we introduce Acoustic Tweezers-Assisted Biomaterial Molding in Petri Dishes (TAMP), enabling tissue fabrication with controlled cellular and ECM architectures in Petri dishes, specifically, producing constructs with customized ECM geometries and various internal cellular architectures, including parallel elongated cell bundles, arrays of interconnected cell spheroids, and lattice-like cellular networks. TAMP leverages a portable acoustic array that delivers standing waves into a Petri dish or a polydimethylsiloxane (PDMS) mold, thereby enabling a unique "dual-control" mechanism. The acoustic field arranges internal cells into parallel line-like and lattice-like patterns, while the PDMS mold defines the overall ECM geometry. Our approach was demonstrated by arranging micro-objects into various patterns within different-shaped molds and fabricating glioma tissues with various unique internal cellular architectures, including parallel elongated glioma tissue bundles, lattice-like glioma tissue networks, and chains of interconnected glioma spheroids. We anticipate the TAMP technique will lead to portable, easy-to-operate tools for engineering tissues with controlled cellular and ECM architectures for biomedical research, disease modeling, and drug testing.

Keywords:  acoustic tweezers‐assisted tissue engineering; elongated glioma tissue bundles; engineered glioma tissue networks; interconnect glioma spheroid chains; tissues with controlled cellular and matrix architectures

DOI:  https://doi.org/10.1002/smll.74599
Nature. 2026 Jul 22.

AI-redesigned starting points and outcomes enhance protein evolution.

Nicholas A Krasnow, Joy A Xu, Emily Zhang, Gandhar K Mahadeshwar, Y Allen Tao, Julia McCreary, Colin F Hemez, Logan E Brown, Wei Jiang, David R Liu.

Engineered or laboratory-evolved proteins often have suboptimal stability, activity or specificity. Here we applied artificial intelligence (AI)-based protein sequence design to address challenges in experimental enzyme evolution. Using the model ProteinMPNN, we redesigned three distinct botulinum neurotoxin (BoNT) proteases, generating variants with improved stability and full catalytic efficiency1. We hypothesized that redesigned enzymes may be more mutationally robust than their wild-type (WT) counterparts, and therefore may serve as better starting points to evolve new function. We performed side-by-side phage-assisted continuous evolution campaigns initiated with AI-redesigned proteases or with the corresponding WT proteases2. Evolving three distinct redesigned enzymes as starting points consistently yielded proteases with higher activity than evolving WT proteases in the same selection. Across four evolution campaigns, redesign conferred robustness that unlocked access to otherwise inaccessible highly functional sequences, confirmed by the inability of redesign-evolved mutations to function in WT enzyme backgrounds. When redesign raises fitness in sequence space local to the starting point, redesigned starting points adapt at a faster rate. Finally, we evolved both WT and AI-redesigned BoNT/E protease to selectively cleave the therapeutically relevant protein ataxin-2. Proteases evolved from the redesigned starting point reached higher catalytic efficiency and stability while minimizing native substrate cleavage, achieving more than 79-fold greater selected specificity for ataxin-2 than the best-performing variant evolved from WT BoNT/E. This study establishes a practical workflow using AI-redesigned starting points to evolve enzymes with improved properties compared with those evolved from natural proteins, with broad implications for protein science.

DOI: https://doi.org/10.1038/s41586-026-10820-0
Nat Commun. 2026 Jul 18.

Engineering microbial consortia for distributed signal processing.

Katherine E Duncker, Ashwini R Shende, Irida Shyti, Ashley Ruan, Ryan D'Cunha, Harshitha Venugopal-Lavanya, Helena R Ma, Sizhe Liu, Neil Gottel, Deverick J Anderson, Claudia Gunsch, Lingchong You.

A central goal in biology is to infer input signals from measurable readouts. Engineered biosensors are usually built to respond selectively to single inputs, so crosstalk between sensors must be removed through laborious, context-specific orthogonalization. Here we show that multiplexed concentrations can be inferred without eliminating crosstalk. We distribute sensing across a microbial community and decode its time-resolved collective response, which can disambiguate combinations of chemical inputs even when individual sensors show crosstalk or respond indirectly. A computational framework coupling kinetic modeling with machine learning maps these community dynamics to input concentrations. We demonstrate quantitative inference in communities with low or high sensor crosstalk, in communities that respond only indirectly to antibiotic combinations, and in pooled hospital sink water spiked with target analytes. By tolerating non-orthogonal, cross-reactive, and indirect responses, distributed dynamic sensing broadens the range of biological systems usable for multiplexed measurement, wherever input combinations produce reproducible, distinguishable response trajectories.

DOI: https://doi.org/10.1038/s41467-026-75739-6
Sci Adv. 2026 Jul 24. 12(30): eaed0971

Neuromorphic tissues: Soft biomolecular networks for brain-inspired temporal computing.

Nicholas X Armendarez, Ahmed S Mohamed, Md Sakib Hasan, Joseph S Najem.

Brains achieve extraordinary efficiency in processing temporal information through dense interconnectivity and recurrent feedback among neurons. Inspired by this principle, we introduce neuromorphic tissues-soft biomolecular networks comprising cell-sized aqueous compartments interconnected by lipid membranes containing voltage-gated ion channels. When a compartment is electrically stimulated by current injection, the membranes separating it from neighboring compartments polarize until channel activation occurs, transiently transforming the interface into a conductive synapse that couples adjacent nodes. These dynamics generate intrinsic physical recurrence, enabling the network to encode, propagate, and reconstruct time-dependent signals without external feedback circuitry. Experiments and modeling demonstrate nonlinear, fading-memory, and recurrent dynamics characteristic of reservoir computing, enabling accurate prediction of nonlinear and chaotic sequences such as NARMA-10 and the Lorenz attractor. This work suggests that spatial interconnectivity can enhance the computational capabilities of physical reservoirs and highlights soft, self-assembled materials as a promising platform for implementing such interconnected systems.

DOI: https://doi.org/10.1126/sciadv.aed0971
ACS Chem Biol. 2026 Jul 20.

Chemically Responsive Protein Switches for the Precise Control of Biological Activities.

Jaime Franco Pinto, Naama Drahy, Séverine Divoux, Franck Perez, Arnaud Gautier.

Controlling the proximity or interaction of proteins with small molecules enables researchers to chemically regulate cellular functions. Here, we leveraged CATCHFIRE (chemically assisted tethering of chimera by fluorogenic induced recognition)─a technology enabling the chemical induction of dimerization in a reversible manner─to create chemically responsive protein switches for the precise and reversible control of various biological activities. CATCHFIRE allowed us to chemically induce the assembly and thus function of various split enzymes─including luciferases, proteases, and DNA recombinases. We extended this approach to develop CATCH-ON, a chemically inducible gene expression system relying on the chemically induced dimerization of the DNA-binding domain GAL4 and the truncated transcription factor p65Δ. CATCH-ON allowed us to precisely regulate the expression of cellular enzymes such as proteases, DNA recombinases, or suicide switches, as well as to control the secretion of therapeutically relevant proteins such as insulin. We showed that the CATCH-ON system is fast-acting, reversible, titratable, nontoxic, and compatible with other chemically induced dimerization systems, opening exciting possibilities for its application in basic research, biotechnology, and cell therapy.

DOI: https://doi.org/10.1021/acschembio.6c00360
ACS Nano. 2026 Jul 21.

DNA-FLASH─a DNAzyme Walker-Based Nanosensor for Digital Biosensing at the Point of Care.

Seppe Driesen, Dries Vloemans, Gangamallaiah Velpula, Céline Van Leemput, Mirjam Kümmerlin, Achillefs N Kapanidis, Cláudio Pinheiro, An Hendrix, Steven De Feyter, Karen Leirs, Jeroen Lammertyn.

  The convergence of biosensing and nucleic acid (NA) nanotechnology represents an opportunity for the development of diagnostic technologies. By harnessing the programmability of nucleic acids, we can design biosensors that offer advantages in stability, scalability, versatility and sensitivity, compared to protein-based systems. In this work we introduce DNA-FLASH (DNA-based FLuorescence Amplification upon Single-target Hybridization), a DNA nanosensor concept for digital biosensing. DNA-FLASH leverages fluorescence amplification by a multicomponent NA enzyme (MNAzyme)-driven DNA walker mechanism on a DNA origami disk. Using super-resolution microscopy and single-molecule photobleaching, we demonstrate reproducible fabrication of DNA-FLASH nanosensors with 12 fluorophore-quencher substrates on a ring-shaped track, surrounding a single MNAzyme walker. This nanoarchitecture enables single-molecule detection of DNA targets down to picomolar concentrations. Through precise patterning of DNA-FLASH nanosensors in arrays on glass, we facilitate high-throughput single-molecule readout. We successfully demonstrate DNA-FLASH in human plasma samples and on an in-house developed, fully integrated, self-powered, disposable microfluidic chip, highlighting its potential use in point-of-care settings. Altogether, DNA-FLASH may support the development of next-generation biosensors capable of addressing pressing global challenges, including rapid disease detection, environmental sustainability, and personalized healthcare.

Keywords:  DNA nanotechnology; DNA origami; biosensing; diagnostics; nucleic acid enzymes; point-of-care detection; self-powered microfluidics

DOI:  https://doi.org/10.1021/acsnano.6c04121
Carbohydr Polym. 2026 Sep 15. pii: S0144-8617(26)00660-0. [Epub ahead of print]388 125543

Bioengineering toughened, stretchable bacterial cellulose-based films inspired by spider silk.

Cristina Campano, Benjamin Schmuck, Maria-Tsampika Manoli, Ana M Hernández-Arriaga, Anna Rising, M Auxiliadora Prieto.

  Bacterial cellulose (BC) has emerged as a promising sustainable biomaterial with potential across multiple fields. However, its intrinsic stiffness and limited toughness restrict its use in applications such as textiles or wearable devices. Spider silk is one of nature's toughest materials, combining high strength and extensibility. The recombinant mini-spidroin (A3I)3-A14, a minimized synthetic variant of a spider silk protein, can be spun under mild conditions into ductile and tough fibers. Here, we present a bioinspired strategy to toughen BC with (A3I)3-A14 by tuning the incorporation route and protein conformation to achieve lower stiffness, higher extensibility, and improved energy dissipation. A motile strain, E. coli JM109 (DE3), was used as a heterologous production host and active delivery vehicle to introduce the mini-spidroin within the BC hydrogel. Guided by glucose-gradient-driven colonization of the porous BC nanofiber network, followed by controlled sodium dodecyl sulfate (SDS)-alkali-mediated cell lysis, this approach enabled deeper in situ incorporation of (A3I)3-A14 within the BC matrix. The resulting BC-silk composites exhibited an >240% increase in toughness, primarily driven by a significant enhancement of the strain at break. This balanced combination of softness, strain tolerance, and energy absorption highlights the potential of BC-silk composites as crease-resistant bio-based films.

Keywords:  Bacterial cellulose; Bioinspired; Colonization; Mini-spidroin; Silk; Toughness

DOI:  https://doi.org/10.1016/j.carbpol.2026.125543
Mater Today Bio. 2026 Aug;39 103443

Redefining 3D cell culture: Human methacryloyl platelet lysates hydrogels for reliable, consistent, and ethical applications.

Mariana M Dias, Ana T Rufino, Rui Vitorino, Catarina A Custódio, João F Mano.

  The transition to human-derived biomaterials is critical for advancing ethical and clinically relevant three-dimensional (3D) cell culture systems. In this study, we evaluate the performance of human methacryloyl platelet lysates (hPLMA), a xeno-free, human-derived hydrogel, benchmarking it against Matrigel, the gold standard in the field, and a widely used but animal-derived matrix with an unethical tumor origin. Human adipose-derived stem cells (hASCs) were encapsulated in both materials and cultured for 14 days. Both materials support high viability and proliferation for 7 days. However, hPLMA promotes consistent cell growth and intricate networks, while Matrigel induces rapid spreading, leading to massive cell clusters and ultimately the degradation of the hydrogel after 7 days. Although macrophage culture in both materials show low cytokine levels, the transcriptomic profile of hASCs in Matrigel reveal a constant high expression of immune-related genes, especially after 5 days. In contrast, hASCs in hPLMA have lower expression of immune response genes and higher expression of genes associated with cell migration, adhesion, and matrix organization, showing hPLMA's ability to mimic the natural cell environment. These results position hPLMA as a robust, xeno-free platform not only for 3D cell culture applications such as drug screening, organ-on-chip and tissue models, but also as a promising candidate for therapeutic applications, including tissue engineering and regenerative medicine. Ultimately, its human origin enhances physiological relevance while minimizing immune activation, supporting its translation towards clinical use.

Keywords:  Human methacryloyl platelet lysates (hPLMA); Hydrogels; Immunogenicity; Matrigel; Transcriptomic analysis; Xeno-free

DOI:  https://doi.org/10.1016/j.mtbio.2026.103443
Adv Mater. 2026 Jul 22. e73765

Highly Entangled Bottlebrush Polymer Networks.

Myoeum Kim, Baiqiang Huang, Shiwang Cheng, Li-Heng Cai.

Entanglements are topological constraints that govern the dynamic mechanical behavior of polymer networks. Linear polymers inevitably entangle at relatively low molecular weights, whereas bottlebrush polymers-consisting of a long backbone densely grafted with many relatively short side chains-suppress entanglements, enabling solvent-free networks with tissue-like softness. Yet, the same steric crowding pre-strains the backbone and renders such networks brittle. Here, we report highly entangled bottlebrush elastomers that combine extreme softness and toughness. Using short polyethylene glycol side chains, we synthesize high molecular weight bottlebrush polymers (>3 × 106 g/mol) that remain amorphous at room temperature. We identify an entanglement threshold of 2.4 × 106 g/mol with an entanglement modulus of ∼1.3 kPa, nearly 1000 times lower than that of linear counterparts. While unentangled bottlebrush networks exhibit strain-stiffening, entangled bottlebrush networks display pronounced strain-softening followed by delayed stiffening due to entanglement slippage. Despite their low modulus (∼1 kPa), these elastomers stretch up to ∼1800% and show a fatigue threshold of ∼63 J/m2, comparable to natural rubber. Their intrinsic fatigue strength-fatigue threshold normalized by modulus-surpasses that of highly entangled linear polymer networks by >40-fold. These results establish a new class of soft yet tough polymer networks and provide a model system for understanding nonlinear mechanics in architecturally complex polymers.

DOI: https://doi.org/10.1002/adma.73765
ACS Appl Mater Interfaces. 2026 Jul 21.

Model-Assisted Prioritization of Gelatin Methacryloyl (GelMA) Hydrogel Formulations for Three-Dimensional Cell Culture.

Peisong Yin, Xin Wang, Suqing Liu, Yujun Huang, Meiyi Huang, Yu Zhang, Ruijun Peng, Jingwen Sun, Yaobin Wu, Ling Wang.

  Owing to highly tunable mechanics, gelatin methacryloyl (GelMA) hydrogels are widely exploited for three-dimensional (3D) cell culture, whereas limited experimental sampling restricts efficient formulation screening. In this work, we developed a BNN-based modeling pipeline to map GelMA hydrogels with various cross-linking parameters toward linear viscoelastic moduli and nonlinear critical stress, thereby categorizing all tested formulations into low/intermediate/high stable mechanical windows. Calibration on C2C12 myoblast morphologies confirmed that nonlinear critical stress complements linear rheological parameters to refine the screening priority of cell-compatible hydrogel recipes. Subsequent validation with primary cardiomyocytes demonstrated consistent morphological trends matching the predefined mechanical windows, alongside ambiguous boundary formulations. Our findings construct a bounded prioritization strategy to rapidly select GelMA compositions under sparse experimental conditions, with further prospective validations demanded before generalized predictive use for diverse tissue engineering scenarios.

Keywords:  Gelatin methacryloyl (GelMA); Hydrogels; Mechanical windows; Rheology; Three-dimensional cell culture

DOI:  https://doi.org/10.1021/acsami.6c11606
Proc Natl Acad Sci U S A. 2026 Jul 28. 123(30): e2610914123

Why shear adhesion is not monotonically enhanced by stiffening.

Zihao Du, Linghao Kong, Ronghao Bao, Huajian Gao, Weiqiu Chen, Changhong Linghu.

  Interfaces between dissimilar elastic materials are ubiquitous in biological and engineered systems and often span orders of magnitude in stiffness. Yet it remains unclear whether stiffening an adhesive system strengthens or weakens shear adhesion, as conflicting trends have been widely reported and the underlying physics has remained unresolved. Here we provide a mechanistic explanation by developing a unified framework for shear adhesion across broad modulus contrasts. We derive an analytical solution for a finite-height elastic adhesive bonded to an elastic substrate and validate the theory using systematic experiments and finite element simulations. We show that, despite global shear loading for the typical geometries encountered, interfacial failure is governed by edge-initiated separation dominated by opening-mode fracture within a finite cohesive zone, rather than by interfacial sliding. Across more than six orders of magnitude in shear modulus contrast, shear adhesion exhibits a pronounced nonmonotonic dependence on stiffness, characterized by well-defined local maxima and minima that delineate attachment- and detachment-favorable regimes. This behavior arises from a competition between a modulus-contrast-dependent corner stress singularity, which promotes separation initiation, and elastic deformation, which controls interfacial opening. Building on this mechanism, we construct parameterized adhesion maps that identify optimal modulus ratios for robust attachment and on-demand release. These results reconcile disparate experimental observations by revealing their common physical origin, establish modulus contrast as an independent design variable for shear adhesion, and provide predictive guidelines for designing bioinspired, wearable, and robotic adhesive systems.

Keywords:  broad modulus contrast; dissimilar elastic materials; nonmonotonic dependence; shear adhesion; unified mechanical framework

DOI:  https://doi.org/10.1073/pnas.2610914123
Proc Natl Acad Sci U S A. 2026 Jul 28. 123(30): e2607437123

Mechanostereochemical modulation of polymer mechanical properties.

Yi Ding, Wei You, Guoquan Liu, Jingxi Deng, Wenbin Wang, Peitong Li, Yongming Wang, Ruixue Bai, Wei Yu, Zhaoming Zhang, Xuzhou Yan.

  Stereochemistry profoundly affects the physical and mechanical properties of polymers, illustrated by the contrast between elastic natural rubber (cis-polyisoprene) and the stiffer, less extensible gutta-percha (trans-isomer). Traditional stereochemistry such as tacticity and cis/trans isomerism primarily governs polymer properties based on fixed structural or conformational factors. Herein, by incorporating the mechanostereochemistry concept into polymers, we demonstrate a stereochemistry paradigm wherein dynamic isomers dictate material properties, thereby defining the unprecedented transient-stereostructure-efficacy mechanism. Specifically, we engineer two mechanically interlocked networks based on [c2]daisy chains, where force-triggered intramolecular motion generates mechanostereoisomers with distinct geometric configurations: [c2]Daisy chain 1 in MIN-1 contracts into a fisherman's knot, whereas [c2]daisy chain 2 in MIN-2 extends into a loop. Due to reduced network elasticity from the loop structure, MIN-2 exhibits a lower modulus in large-strain shear measurements and less pronounced strain hardening in tensile tests compared to MIN-1. Since these mechanostereoisomers are induced by force, material properties show strain-dependent character: both networks perform similarly under small or no strain, but diverge significantly at large strains. Our work expands the conceptual boundaries of polymer stereochemistry and provides insights for designing high-performance materials through stereochemical control.

Keywords:  force-induced isomerization; mechanical property; mechanically interlocked structures; mechanostereochemistry; transient stereostructure

DOI:  https://doi.org/10.1073/pnas.2607437123
Metab Eng. 2026 Jul 24. pii: S1096-7176(26)00103-5. [Epub ahead of print] 102508

Engineering a Gluconate Bypass Carbon Entry Architecture for Robust Stationary Phase Biomanufacturing.

Utsuki Yano, Payel Sarkar, Michael D Lynch.

Two-stage bioprocesses which decouple cell growth from product synthesis are an attractive approach to biomanufacturing. However high levels of production in stationary phase cultures often suffer from a progressive decline in metabolism. We demonstrate that in E. coli pyruvate accumulation, an inevitable consequence of high-flux metabolism, acts as a major inhibitor of stationary-phase glucose uptake. To address this limitation, we introduce a redesigned central metabolic architecture, the gluconate-bypass (GBP), which reroutes carbon flux around glucose-6-phosphate to sustain metabolic activity during stationary phase production. This architecture provides two key advantages: it decouples glucose uptake from pyruvate mediated inhibition, enabling prolonged stationary phase productivity, and glucose oxidation intrinsically co-generates the reducing cofactor NADPH to support biosynthetic pathways that require NADPH. We validated this architecture using the NADPH dependent production of L-alanine as a representative case study. Implementation of the GBP metabolism generated a self regulating host that achieved a record alanine titer of 197 g L-1 and extended production longevity by 1.6 fold, resulting in an improved production yield of 94%. Together, these results demonstrate that the GBP metabolism supports robust stationary phase biosynthesis and provides a versatile framework for efficient production of pyruvate derived chemicals.

DOI: https://doi.org/10.1016/j.ymben.2026.102508
Small. 2026 Jul 24. e74687

Geometry-Encoded Programmable Mechanics in Single-Material Dual-Phase Metamaterials.

Miao Zhao, Na Qiu, Xuhui Zhang, Bei Peng, Zhi Zeng, Xinwei Li, Qing Li.

  Programmable metamaterials that exhibit prescribed mechanical responses and adaptive deformation under external loading are highly desirable for multifunctional engineering applications. However, most existing designs rely on multi-material systems, which pose significant fabrication challenges with conventional additive manufacturing. Inspired by the unique soft-hard heterogeneous architecture of nacre, this study introduces a novel class of dual-phase (DP) metamaterials where spatially encoded soft and hard phases are realized through bending-dominated and stretching-dominated lattice architectures, respectively. By systematically varying the spatial coding patterns of soft-hard phases, representative DP metamaterials are shown to exhibit programmable nonlinear mechanical responses and tailored failure processes, achieved through geometry-based mechanical encoding governed by phase interactions and internal stress redistribution. Notably, the engineered sequenced failure processes and phase-coupling-induced strengthening effects lead to significantly enhanced energy absorption compared with the constituent architectures, while enabling customizable plateau stress. To efficiently explore the vast design space of DP metamaterials, a data-driven framework is then developed to model the relationship between spatial encodings and nonlinear mechanical responses. The trained model enables rapid and accurate inverse design of DP metamaterials matching the complex target responses for multifunctional applications. Overall, this work establishes a new geometry-based strategy for achieving highly programmable mechanical responses in single-material metamaterials.

Keywords:  additive manufacturing; inverse design; machine learning; metamaterial; programmable mechanical property

DOI:  https://doi.org/10.1002/smll.74687
Adv Mater. 2026 Jul 22. e74162

Photoactivable Surfactant Design for In Situ Stabilization of Hydrogel Bioelectronics.

Seungyeon Lee, Donggyun Lee, Soo-Hwan Lee, Yuri Lee, Jooyeun Chong, Gunho Chang, Hyunjun Kim, Aejin Kim, Kyung Su Kim, Jahyun Koo, Hyojin Lee, Jiheong Kang.

  Conductive polymer hydrogels offer unique advantages for soft, stretchable biointerfaces by combining tissue-like mechanics with high ionic conductivity. However, their reliable integration with hydrophobic substrates and encapsulants essential for electrical insulation and chemical protection remains a major challenge due to poor wetting and interfacial delamination in aqueous environments. Here, we report a facile strategy for the in situ stabilization of conductive polymer hydrogels on hydrophobic substrates using a photoactivable surfactant (PAS). PAS reduces interfacial surface energy and, upon UV activation, forms covalent bonds with stretchable substrates, thereby yielding strong adhesion and long-term stability under wet conditions. This molecular design also enables photopatterning of hydrogels without compromising performance. Notably, PAS not only stabilizes and patterns conductive hydrogels in situ but also enhances their mechanical and electrical properties. PAS-integrated hydrogel biointerfaces exhibit robust operation in aqueous environments and demonstrate reliable in vivo electromyographic (EMG) signal recording, underscoring the potential of this approach for next-generation implantable and wearable bioelectronics.

Keywords:  adhesion; bioelectronics; covalent bond; delamination; materials science; nanotechnology; surface energy; surfactant; wetting

DOI:  https://doi.org/10.1002/adma.74162
Nanoscale Adv. 2026 Jul 09.

Development and characterization of LipoCatch: a bacterial lipoprotein-based biomaterial that self-assembles into nanostructures.

Francesca A Starvaggi, Claire J Stewart, Marc A Arslanian, Matthew A Treviño, Scott A Weston, Naima G Sharaf.

Genetically encoded nanomaterials enable the control of molecular composition and function, yet the use of the biosynthetic bacterial lipidation pathway to build hybrid protein/lipid nanostructures has not been reported. Here, we designed a versatile bacterial lipoprotein, named LipoCatch, for modular nanostructure formation. Lipidation was achieved by appending a signal peptide to the protein-encoding gene of SpyCatcher from the SpyCatcher/SpyTag protein/peptide binding pair. This protein was biosynthetically produced in E. coli and purified in the presence of detergent. LC-MS, SEC, DLS, and TEM confirmed site-specific lipidation and formation of nanoparticles with an average diameter of 13 nm. We show that LipoCatch supports two orthogonal functionalization strategies: (1) covalent modification through the SpyCatcher/SpyTag system and (2) the non-covalent incorporation of phospholipids that permits the tuning of particle size and compositions. Finally, stability studies show LipoCatch and hybrid LipoCatch/phospholipid nanostructures are tolerant to lyophilization, in contrast to phospholipid-only liposomes. Together, this proof-of-principle study establishes an engineered bacterial lipoprotein, LipoCatch, as a genetically encoded platform for building customizable bacterial lipoprotein-based biomaterials.

DOI: https://doi.org/10.1039/d6na00554c
Small. 2026 Jul 24. e74628

Water Droplet Hammer: Piezoelectric Sensing of Ultrafast Mechanical Transients During Droplet Impact.

Ian Kim, Chen Lin, Zuer Wu, Siyuan Rao, Qianbin Wang.

  Erosion and fracture caused by repeated water-droplet impacts are often attributed to splash-mediated material removal, high-pressure impulsive loading, or cavitation. Yet, the mechanical response during the earliest instant of impact remains difficult to capture. Using a high-temporal-resolution polyvinylidene fluoride (PVDF) piezoelectric sensor combined with high-speed imaging, we directly measure substrate-coupled mechanical transients during a single water-droplet impact. A strong impulsive strain response appears within the first 2 ms after contact, followed by coherent 100-500 Hz oscillations at the water-solid interface during the first 20 ms, before any rebound occurs. The oscillation frequency is modulated by an effective interfacial stiffness, whereas the impulsive peak-to-peak response scales with droplet size and impact velocity. The experimentally captured signals provide direct experimental evidence of ultrafast substrate-coupled mechanical transients during droplet impact and establish a minimal inertial-capillary framework for understanding mechanical signatures that may contribute to low- to moderate-speed droplet-induced erosion and fatigue.

Keywords:  PVDF piezoelectric sensing; droplet impact; interfacial oscillation; substrate‐coupled strain; superhydrophobic surface

DOI:  https://doi.org/10.1002/smll.74628