bims-enlima Biomed News
on Engineered living materials
Issue of 2026–05–10
39 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool



  1. Sci Adv. 2026 May 08. 12(19): eaee3907
      Bioluminescence offers a powerful tool for real-time, label-free sensing for living materials. However, conventional approaches often rely on mechanical stimulation, which is difficult to standardize, localize, and sustain. Here, we introduce a chemical strategy to stimulate and sustain bioluminescence in the marine dinoflagellate Pyrocystis lunula, enabling durable, adaptive, light-emitting living materials. By embedding P. lunula into 3D-printed, alginate scaffolds, we engineered architecturally stable constructs with long-term cellular retention, viability, and light-emitting capacity. Exposure to acidic and basic environments produced chemically encoded bioluminescent signatures: Acid triggered localized, persistent emission, while base induced diffuse, biphasic emission indicative of cellular stress. Notably, combining chemical and mechanical stimulation led to enhanced total bioluminescence emission, achieving greater amplitude and duration of light emission without compromising cell mechanoresponsiveness. Longitudinal studies over 4 weeks demonstrated that our materials retain responsiveness and structural integrity across repeated stimulation cycles, overcoming single-use limitations. Together, these findings establish a chemistry-controlled platform for light-emitting living materials for biosensing, soft robotics, and environmental monitoring.
    DOI:  https://doi.org/10.1126/sciadv.aee3907
  2. Sci Adv. 2026 May 08. 12(19): eaed1774
      Reconfigurable mechanical systems enable precise programmable control over structural properties, expanding opportunities in architected materials, adaptive devices, and multifunctional structures. Here, we introduce elastic rod origami (RodOri), a platform that exploits remarkably simple elements-prestressed, naturally curved rods-into a system with an extraordinary degree of multistability and configurational richness. For example, a single six-rod RodOri unit can easily access 11 distinct configurations, far exceeding the reconfigurability of conventional origami or general mechanical reconfigurable systems. Individual rods, constrained under clamped boundary conditions, undergo transitions between discrete morphologies whose strain energy and stiffness are precisely prescribed by their natural curvature. Assembling these rods into modular multirod architectures yields metamaterials with numerous stable configurations that can be selectively and reversibly programmed. This configurational diversity enables tunable static stiffness and nonlinear force response, thus enabling tunable dynamic behaviors such as vibration filtering, wave propagation switching, and mode conversion within a single, easily manufactured platform. By leveraging curvature-induced mechanical instability, RodOri unlocks highly programmable static and dynamic mechanical behavior, offering tailorable design strategies for reconfigurable structures, soft robotics, medical devices, and adaptive materials.
    DOI:  https://doi.org/10.1126/sciadv.aed1774
  3. Biofabrication. 2026 May 02.
      Viscoelastic hydrogels crosslinked by dynamic bonds hold great promise for mimicking the matrix dynamics of native tissues in cell culture and tissue engineering. Yet, their application in light-based bioprinting remains largely unexplored due to the incompatibility between reversible bond formation and photocrosslinking. This study addresses this key challenge by presenting a new class of photocrosslinkable, hydrazone-based bioinks developed from two modified polymers (Gel-A-DAAM and Gel-C-DAAM). These polymers are designed to enable reversible bond formation within hydrogel networks by attaching polymerizable groups to the polymer backbone via modular hydrazone conjugation chemistry. The resulting materials exhibit distinct mechanical properties depending on their hydrazide substituent, swelling medium, incubation temperature, and incubation time. Storage moduli of produced hydrogels vary between 0.08 - 1.2 kPa, which spans multiple scales of physiologically relevant tissue environments. The novel bioinks are suitable for droplet-based bioprinting followed by light-based crosslinking, and support cell spreading of human fibroblasts. Notably, the morphology of encapsulated cells varies with different hydrazide substituents, highlighting the potential of the developed bioink system to systematically investigate cell-matrix interactions. The combination of biological tunability and printability positions this system as a promising platform for fabricating next-generation tissue-mimetic constructs using advanced bioprinting technologies.
    Keywords:  biofabrication; dynamic hydrogel; mechanobiology; photocrosslinking; polymer networks; tissue engineering
    DOI:  https://doi.org/10.1088/1758-5090/ae67a6
  4. Nat Commun. 2026 May 06.
      Engineered microbial consortia are emerging as programmable systems capable of sensing and responding to their environment. However, maintaining defined community composition over time remains challenging, particularly in bioprocesses where growth conditions and metabolic burdens continuously shift. Here, we develop a burden-aware multicellular RNA-based feedback control system that stabilises coculture composition by coupling gene expression burden to growth regulation. The system integrates three modules: quorum sensing-based communication, an RNA-based comparator computing deviations from a target ratio, and tuneable growth regulation via heterologous expression burden or CRISPRi-mediated knockdowns. In a two-strain E. coli coculture, this architecture maintains stable coculture ratios over 24-hour batch cultures, recovers growth rates by up to 90% following burden-induced growth reduction, and increases protein production yields by up to 81% in the slower-growing strain. We achieve tuneability by adjusting RNA binding strength and quorum-sensing signal production. This work demonstrates that burden-driven growth control can be used to stabilise and tune synthetic microbial consortia.
    DOI:  https://doi.org/10.1038/s41467-026-72389-6
  5. Adv Sci (Weinh). 2026 May 07. e24319
      Cells in many naturally occurring organisms routinely cooperate to control their extracellular pH in a dynamic and reversible manner, but this capability has been underexplored in synthetic biology. Here, we sought to engineer a microbial system that switches between two states -high and low extracellular pH- with minimal human intervention. We accomplished this by combining: (1) a genetic circuit that produces recombinant urease under the control of a light-inducible promoter; (2) a degradation tag on urease to accelerate the high-to-low pH transition; and (3) optimization of several environmental factors, including media composition, replenishment rate, and light exposure patterns. The system raises the pH when urease is produced and hydrolyzes urea in the media to produce ammonia; it lowers the pH as a byproduct of the cell's native metabolism when urease production ceases. We demonstrate that the optimized system cycles continuously for up to 14 days with minimal performance loss. Overall, our system demonstrates synthetic pH control in an engineered living system and highlights challenges and potential solutions for using such systems outside of the context of typical laboratory manipulation.
    Keywords:  deployable living systems; engineered living material; light‐responsive bacteria; optogenetics; pH modulation
    DOI:  https://doi.org/10.1002/advs.202524319
  6. Angew Chem Int Ed Engl. 2026 May 06. e4174230
      Synthetic cells, assembled from defined molecular components, are designed to mimic the features, form, and function of living cells. Light has emerged as a uniquely precise, biorthogonal, and non-invasive stimulus for regulating and energizing these systems, enabling chemical inhomogeneity and an out-of-equilibrium state central to many cellular processes. This review highlights the biological behaviors and functions that light has helped recreate in synthetic cells, including compartmentalization, energy supply and metabolism, protein synthesis, communication, growth, shape change and division, and motility. We survey the breadth of light-responsive components incorporated into synthetic cells, spanning photoswitchable and photocleavable small molecules, photoswitchable proteins, photocatalysts, nanoparticles, and photosynthetic organelles or organisms. Finally, we offer a perspective on key design considerations such as wavelength, reversibility, integration, biocompatibility, multicolor regulation, and biohybrid strategies. Together, these advances chart promising routes toward more dynamic, energy-autonomous, and programmable synthetic cells that will deepen our understanding of cellular functions and enable emerging biotechnological applications.
    Keywords:  light; photoswitchable; spatiotemporal regulation; synthetic biology; synthetic cells
    DOI:  https://doi.org/10.1002/anie.4174230
  7. Biotechnol Adv. 2026 Apr 30. pii: S0734-9750(26)00118-7. [Epub ahead of print] 108912
      Filamentous fungi have played an undeniable role in the biosphere for hundreds of millions of years and, for humans, have increasingly been developed as sources of food, medicine and other resources; their uses growing to include materials science and bioremediation. As these developments have gained pace, a variety of disparate fields are making new advances and turning to synthetic biology to increase their potential. As genetic sequencing and computing technologies widen our knowledge of the different species of fungi, synthetic biology enables us to harness and expand their unique traits. These developments are discussed in the context of these existing and emerging applications of engineering and synthetic biology, so that they might be more widely understood, thus promoting the standardisation of language and innovation. Certain challenges and research gaps within the investigated research fields are also highlighted, as are various opportunities and connections found during the exploration of these fields, and the impact of developing technologies including 3D printing and cell-free systems.
    Keywords:  3D Printing; Biomaterials; Bioreactors; Bioremediation; Engineered living materials; Fungi; Mycoelectronics; Myconanotechnology; Synthetic Biology
    DOI:  https://doi.org/10.1016/j.biotechadv.2026.108912
  8. Chem Commun (Camb). 2026 May 05.
      In the 21st century, bioinspired hydrogels have been developed using stimuli-responsive polymer networks in aqueous environments. In this review, "metabolism-inspired hydrogels" are discussed, focusing on the symbolic functions of living organisms. Considering that cell activities in animals and plants are driven by cyclic chemical reactions such as TCA cycle or Calvin-Benson cycle, catalyzed by multiple enzymes, we discuss artificial hetero-systems, especially, self-oscillating gel and artificial photosynthetic gel designs. By providing the necessary materials or photoenergy to gels, they can be converted into useful substances or mechanical energy. These gels can be categorized as chemomechanical or energy-converting gels. Copolymer networks with a redox catalyst convert substances and energy by acting as an active network during the phase transition of the polymer. The polymer itself is not necessary for the chemical reactions, but it acts as a critical active mediator for the emergence of function. To construct polymer networks, functional molecules or catalytic nanoparticles can be integrated using simple methods. This review focuses on the methodology for network design and stepwise integration. In the future, synthetic technologies, such as precise polymerization, are expected to promote a range of self-organized morphologies and efficient energy conversion. We hope that the discussions in this review will help leverage the huge potential of polymer networks in the development of soft materials.
    DOI:  https://doi.org/10.1039/d5cc06562c
  9. Adv Mater. 2026 May 08. e22423
      The hierarchical fiber architecture of tendons, which integrates high fatigue resistance, high water content, and rapid responsiveness to stimuli over millions of annual cycles, makes them an ideal model for long-term wearable intelligent materials. However, synthetic hydrogels prepared via methods such as electrospinning, freeze-thawing, freeze-casting, and solvent exchange, often lack comprehensive structural and functional integration compared to their biological counterparts. To address this challenge, we developed a synergistic fabrication strategy that integrates freeze-thawing, mechanical training, and solvent exchange to construct hierarchically structured hydrogels. The polyvinyl alcohol-based hydrogel that has been repeatedly freeze-thawed, was then immersed in a glycerol/water solvent containing ferric chloride and subjected to approximately 200 000 mechanical training cycles. The resulting hydrogel exhibited remarkable comprehensive properties, including a tensile strength of 9.38 MPa, a fracture energy of 187.5 kJ m-2, a fatigue threshold of 7850 J m-2, a conductivity of 0.64 S m-1, and excellent flexibility even at -80°C. Leveraging this multifunctionality, the hydrogel was further assembled into a strain sensor capable of precise, rapid monitoring of finger motion and was employed in a gesture-controlled drone system. This work provides a universal and effective approach to designing fatigue-resistant hydrogels, offering new insights into the development of next-generation bioinspired, flexible electronic materials.
    Keywords:  anti‐freezing; fatigue resistance; human‐machine interaction; mechanical training; organohydrogels
    DOI:  https://doi.org/10.1002/adma.202522423
  10. Mater Today Bio. 2026 Jun;38 103175
      The design of implantable biomaterials often aims to guide local cell behavior to control immune response. Non-chemical routes exploit the effect of mechanical properties and structure morphology on cell behavior. A class of substrates known as bicontinuous interfacially jammed emulsion gel (bijel)-templated materials (BTMs) exhibit characteristically uniform pore size and surface curvature. Existing research on these materials in vivo demonstrates their ability to modulate the inflammatory response in the anti-inflammatory direction. We investigate a subset of the contributing components to that effect by examining the behavior and phenotype of macrophages within BTMs in vitro. The comparative substrate, the particle-templated material (PTM), has an equivalent chemical composition, but has variable pore size and surface curvature. Macrophages within these two materials take on notably different cell shapes and phenotypes. Macrophages interacting with the BTM exhibit less circular cell shapes and a lower state of inflammation. This effect is significant enough to induce lower pro-fibrotic activation in fibroblasts, without direct BTM-fibroblast contact. These results suggest that microscale curvature and pore size have a direct effect on macrophages, and that this effect can cause phenotypic changes in other cells. Findings reaffirm the significance of targeting macrophages in biomaterials design and support further investigation of the immune signaling cascade that occurs within BTMs. Our contributions to the fundamental knowledge of cell behaviors in these porous materials provide new insights applicable to advancing biomaterials design.
    Keywords:  Bijel; Cell shape; Inflammation; Macrophage; Porous material
    DOI:  https://doi.org/10.1016/j.mtbio.2026.103175
  11. Adv Sci (Weinh). 2026 May 05. e75525
      Slide-ring network (SRN) hydrogels derived from ring-crosslinked polyrotaxanes exhibit exceptional mechanical properties attributable to a pulley effect, whereby mobile-ring crosslinks redistribute tension under deformation through a slip-link mechanism. However, SRN hydrogels weaken severely upon swelling in water, limiting their utility at high water content ( >$>$ 90 wt.%). Here, two distinct physical slip-link mechanisms are combined in a highly entangled slide-ring double network (HESRDN) hydrogel: the pulley effect of a polyrotaxane slide-ring network and the entangled chains of a sparsely cross-linked polyacrylamide network. HESRDN is prepared by photopolymerization of acrylamide/N,N'-methylenebis(acrylamide) within a partially swollen slide-ring hydrogel. The dual slip-link architecture synergistically strengthens and toughens the hydrogel far beyond the sum of the component networks, yielding high work of fracture (1275 kJm-3), toughness (2020 Jm-2), and near-complete reversibility (99.7%) at >$>$ 91 wt.% water. HESRDN withstands continuous friction for over 12 h without rupture, compared to minutes for the SRN and 5 h for the HEN component networks, reflecting the unique capacity of the dual slip-link architecture to delocalize and redistribute stress under sustained mechanical loading.
    Keywords:  double network; high entanglement; hydrogel; slide‐ring gel
    DOI:  https://doi.org/10.1002/advs.75525
  12. Nat Commun. 2026 May 07. pii: 3783. [Epub ahead of print]17(1):
      Sorbent-based atmospheric water harvesting promises passive, geography-independent, and economical freshwater production. Achieving low water cost through moisture harvesting demands inexpensive, high-performance, and durable sorbents. Among all sorbents, hydrogel salt-composites have exceptional performance at a low cost. However, hydrogel durability has so far been overlooked, ultimately preventing moisture capture from realizing reliable, inexpensive water production. In this work, we systematically study hydrogel-salt composite degradation under different conditions. We demonstrate that commonly used polyacrylamide-lithium chloride (PAM-LiCl) are intrinsically durable, with a limited decrease (~50%) in their elastic moduli, even at elevated temperatures (75 °C) and for prolonged durations (>8 months). In contrast, degradation quickly occurs (<3 weeks) when these hydrogels interface with copper and copper oxides, as is common practice in moisture-harvesting devices or for polyvinyl alcohol-lithium chloride hydrogels (in <50 days). We rationalize these results through a proposed metal-mediated degradation mechanism involving hydroxyl radical generation, which is consistent with our PAM-LiCl observations, including ion concentration measurements and experiments with other metals. With the insights from our experiments and proposed mechanism, we implement coatings which prevent hydrogel degradation. This enables stable cyclic moisture absorption-desorption (>190 cycles) and provides a path towards <0.01 $/L water from moisture.
    DOI:  https://doi.org/10.1038/s41467-026-71987-8
  13. bioRxiv. 2026 Apr 26. pii: 2026.04.24.720480. [Epub ahead of print]
      Investigating and manipulating cellular events requires precise control of protein function. To enable control over cellular processes, we set out to design a chemically induced dimerization (CID) system consisting of a de novo designed ligand and protein pair. Here we describe the design of a C2 symmetric membrane permeable macrocyclic peptide and a cognate protein homodimer which binds the macrocycle through a large interface with both chains. The designed homodimer binds the macrocycle with a K D of 36 nM, and the x-ray crystal structure of the protein homodimer-macrocycle complex is very close to the computational design model, with the C2 axis of the macrocycle aligned with the homodimer C2 axis. Transcriptional and split luciferase assays in mammalian cells demonstrates conditional control over both a reporter gene expression and luciferase reconstitution.
    DOI:  https://doi.org/10.64898/2026.04.24.720480
  14. Chem Mater. 2026 Apr 28. 38(8): 4319-4333
      Most organoids are cultured in Matrigel, a complex and poorly defined matrix that limits our mechanistic understanding. Synthetic hydrogels offer a versatile alternative, providing precise control over mechanical and biochemical cues. Using two topologically different types of hydrogel precursors, branched poly-(ethylene glycol) (PEG) and PEG bisdendrons, we have obtained a library of hydrogels via thiol-ene cross-linking with branched PEG-thiol. Their chemical conversion was monitored by Raman spectroscopy, while swelling and mechanical properties, including elastic, viscoelastic, and relaxation parameters, were systematically evaluated. Bisdendron hydrogels dissipate stress through abundant weak interactions, conferring adaptive viscoelastic behavior, an underexplored feature in a 3D culture. To link macromolecular dynamics with bulk properties, polymer chain mobility and internal architecture were probed using MAS solid-state NMR and freeze-fracture cryo-SEM. To introduce bioactivity, RGD peptides were used and immobilized via thiol-ene chemistry, forming spatially organized clusters within the hydrogels. This strategy enables the design of customizable matrices with tunable mechanics, adjustable porosity, and controlled bioactive presentation, closely mimicking native microenvironments. Our platform can provide a chemically defined and versatile toolbox for organoid culturing.
    DOI:  https://doi.org/10.1021/acs.chemmater.6c00419
  15. Mater Horiz. 2026 May 05.
      Adhesive polyphenolic materials, inspired by mussel underwater adhesion, are promising candidates for versatile medical and industrial adhesives. Yet, most synthetic routes remain chemically intensive, energy-demanding, and poorly suited to sustainability and industrial-scale productivity. Conventional EDC/NHS carbodiimide coupling tethering polyphenolic moieties to polymer backbones requires costly reagents, multi-step purifications, and extensive dialysis, waste, and scale-up inefficiency. Here, we introduce a rapid, simple, coupling agent-free synthetic approach to produce adhesive polyphenolic conjugates entirely from renewable resources. Specifically, chitosan-1,2,4-benzenetriol (CHI-B) conjugates were synthesized VIA spontaneous conjugation between fructose-derived biomass, 1,2,4-benzenetriol (BTO), and crustacean-derived chitosan without heating or carbodiimide coupling agents, achieving rapid reaction within 30 minutes at scales reaching tens of liters in a laboratory setting. CHI-B effectively functionalizes challenging substrates such as PTFE and glass, transforming them into large-area superhydrophilic surfaces. Furthermore, CHI-B demonstrated potent hemostatic efficacy in a mouse liver bleeding model, highlighting its potential for biomedical and sustainable industrial applications.
    DOI:  https://doi.org/10.1039/d6mh00249h
  16. Mater Horiz. 2026 May 06.
      Active composites (ACs) capable of autonomous shape transformation under external stimuli enable new opportunities for soft robotics, biomedical devices, and intelligent structures. However, the combinatorial design space of multi-material 3D printing makes inverse design computationally intractable. Here, a reinforcement learning (RL)-based framework is proposed that reformulates the inverse design of thermally active composites (TACs) as a sequential decision-making process. A 4 × 24 grid is decomposed into 24 column-wise decisions to minimize deformation error with respect to target trajectories. A single target design was first demonstrated for an individual trajectory. A target-conditioned policy was then learned using multiple targets to enable rapid design across diverse shapes. The multiple target policy was further transferred to accelerate single target optimization. Performance was evaluated against genetic algorithm (GA) and sequential subdomain optimization (SSO) using the number of samples and function evaluations (FEs) under identical termination criteria. Experimental validation was conducted using 4D-printed TAC specimens via grayscale digital light processing (g-DLP), and demonstrations with complex trajectories, including free-form KAIST logo patterns, confirm that the proposed framework achieves target accuracy (root mean square error ≤ 0.1) with low samples and FEs. This study demonstrates that an RL agent can rapidly perform sequential material design through long-term reward optimization, indicating its potential for extension to intelligent design and manufacturing pipelines.
    DOI:  https://doi.org/10.1039/d6mh00239k
  17. Biomacromolecules. 2026 May 08.
      Biomimetic hydrogels with great mechanical properties that provide stable and low-impedance interfaces are essential for long-term wearable bioelectronics. In this study, we developed dopamine-grafted carboxymethyl cellulose (CMCDA) hydrogel and oxidative cross-linking form (CMCDA'). Using multidimensional (1D/2D) NMR techniques, we provide detailed structural elucidation of dopamine-grafted polysaccharides, offering new insights into amide formation, Schiff base/Michael addition structures, and partially oxidized polydopamine segments. The cross-linked CMCDA' hydrogels are mechanically robust, highly hydrophilic, and strongly adhesive on various substrates, enabling conformal skin contact. After electrolyte exchange with saturated NaCl, CMCDA' becomes ionically conductive (5-10 S m-1) and maintains stable impedance under continuous hydration. Integrated as a wearable electrode interface, CMCDA' supports reliable electrocardiogram acquisition for one week, outperforming the commercial conductive gel at curved body sites. These results highlight oxidative-cross-linked, cellulose-derived hydrogels as sustainable ionically conductive interfaces for long-term wearable bioelectronics.
    DOI:  https://doi.org/10.1021/acs.biomac.6c00288
  18. Curr Opin Chem Biol. 2026 May 04. pii: S1367-5931(26)00042-6. [Epub ahead of print]92 102693
      Bioorthogonal chemistry was originally developed for fast and selective ligation of small molecules onto biomolecules in complex biological environments. Over time, the field has grown significantly beyond just clicking molecules together. It now includes reactions that can form or break chemical bonds and control how reactive substances are generated within living organisms. The field is continuing to develop strategies that allow reactions to be turned on when needed, exhibit greater compatibility in biological environments, and enable multi-step transformations to achieve complex operations. In this review, we summarize these new developments, including new click reactions and reagents, inducible and enzyme-activated click systems, click-induced bond dissociation reactions, bioorthogonal chemical operations, and bioorthogonally activated reactive species.
    DOI:  https://doi.org/10.1016/j.cbpa.2026.102693
  19. Mater Horiz. 2026 May 06.
      The development of self-healing conductors that are simultaneously printable, recyclable, and resilient to severe mechanical damage remains a key challenge for flexible bioelectronic technologies. Here, we report a multifunctional composite based on poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) blended with a custom-designed polyurethane (PU) incorporating dynamic disulfide bonds and hydrogen-bonding motifs. This materials design enables autonomous room-temperature healing from scratches, cuts, and punctures, without external stimuli, while preserving mechanical integrity and electrical continuity. The composite is processable from green solvents and can be spin-coated or printed into uniform, transparent, and highly stretchable films, as well as free-standing membranes transferable to diverse substrates. Optimized PEDOT:PSS/PU/Gly films exhibit a functional conductivity (∼15 S cm-1), high stretchability (>650%), strong self-adhesion, and stable performance under repeated deformation. Importantly, the material supports both mechanical reuse and chemical recycling over at least 15 cycles, retaining more than 90% of its mechanical strength and fully recovering its electrical conductivity. Mechanistic investigations reveal that reversible disulfide exchange and hydrogen bond reformation govern rapid network reorganization and efficient self-repair. Printed electronic tattoos and free-standing electrodes fabricated from this composite deliver low-impedance and high-fidelity electrocardiogram (ECG) recordings. Together, these results establish a sustainable and versatile materials platform that advances self-healing conductors beyond superficial damage, providing a practical pathway toward durable and recyclable bioelectronic materials and devices.
    DOI:  https://doi.org/10.1039/d6mh00177g
  20. Cell Rep Methods. 2026 May 05. pii: S2667-2375(26)00130-X. [Epub ahead of print] 101430
      Antibiotics have saved an untold number of people and animals since penicillin's miraculous discovery in 1928. In the following half-century, progressive discoveries involving antibiotic resistance genes (ARGs), the microorganisms responsible, and their transferrable genetic material have yielded the tools necessary for genetic engineering, birthing the biotechnologies that continue to revolutionize healthcare. After half a century of antibiotic use in the biological sciences, we are, however, faced with an inconvenient question: what happens to residual antibiotics and ARG-containing recombinant DNA after experiments? According to sequencing, we demonstrate that neither severe bleach treatments nor autoclaving completely destroys plasmid-encoded ARGs in bacterial cultures. Furthermore, we show that various bacteria can be transformed using the isolated DNA, confirming that intact plasmids survived these common cell culture disposal methods. This work will catalyze future policy discussions, the development of antibiotic-free selection systems, and continued support for research into the underexplored anthropogenic sources of engineered DNA.
    Keywords:  CP: biotechnology; CP: microbiology; antibiotic resistance; biocontainment; biological waste disposal; biosafety; horizontal gene transfer; recombinant DNA
    DOI:  https://doi.org/10.1016/j.crmeth.2026.101430
  21. Biomater Adv. 2026 Apr 29. pii: S2772-9508(26)00209-8. [Epub ahead of print]186 214911
      Hypoxia remains a major barrier to the viability and function of engineered large tissue constructs. Conventional strategies such as oxygen-releasing biomaterials and pre-vascularization have shown partial success, often constrained by scalability and long-term sustainability. Co-culturing photosynthetic microalgae and animal cells offers an alternative by establishing living oxygen factories that locally convert carbon dioxide into oxygen and thus mitigate hypoxia. Despite the promise of this symbiotic approach, inherent challenges remain, including physiological incompatibilities between microalgae and animal cells, susceptibility to prolonged exposure to light by animal cells, and nutrient competition. In this perspective, we first highlight the potential and challenges of co-cultures between microalgae and animal cells. The discussion is then followed by showcasing experimental strategies for optimizing photosynthetic oxygen delivery in a continuous millimetric three-dimensional extracellular matrix-mimicking environment. Using alginate hydrogel beads containing Chlorella vulgaris and L929 cells, we demonstrate a proof-of-concept in which light-driven oxygenation significantly enhanced animal cell viability and functionality up to 7 days of culture. Relevant setbacks in the replication of results were met between independent experiments, revealing that the proposed hybrid cultures still face difficult-to-control aspects. While emphasizing the need for standardized methodologies and reliable optimal predictors of co-culture performance, our findings strengthen the compatibility of Chlorella vulgaris with animal cells in culture, as well as the potential of microalgae as a sustainable, low-cost, and environmentally friendly oxygen source for the next generation of advanced engineered tissues, in vitro models, and future food systems. Importantly, this study does not aim to achieve sustained oxygen-autonomous constructs, but instead defines the compatibility window, transient benefits, and reproducibility limits of direct microalgae-animal cell co-culture under standard animal culture conditions.
    Keywords:  Chlorella vulgaris; Living materials; Microalgae-animal cell co-culture; Oxygen-generating biomaterials; Photosynthetic microalgae; Photosynthetic oxygenation; Three-dimensional hydrogels; Tissue engineering
    DOI:  https://doi.org/10.1016/j.bioadv.2026.214911
  22. Nature. 2026 May 06.
      
    Keywords:  Chemical biology; Drug discovery; Materials science; Organic chemistry
    DOI:  https://doi.org/10.1038/d41586-026-01155-x
  23. Sci Adv. 2026 May 08. 12(19): eaeb6691
      Nascent adhesions are early integrin-based assemblies that couple the extracellular matrix to the actin cytoskeleton and mature into focal adhesions. Many nascent-adhesion proteins interact through weak, multivalent contacts, suggesting that liquid-like organization may contribute to adhesion assembly. However, how phase separation shapes actin polymerization and organization remains unclear. Here, we compare two vasodilator-stimulated phosphoprotein (VASP)-recruiting adaptor proteins, zyxin and vinculin, to determine how adaptor identity tunes condensate properties and actin coupling. Both zyxin-VASP and vinculin-VASP assemblies drive integrin clustering and support actin filament growth. Notably, zyxin-VASP condensates remain fluid and redistribute along newly formed actin bundles, whereas vinculin-VASP condensates are more rigid and fail to spread along actin despite sustaining polymerization. These results suggest that differential VASP recruitment can modulate condensate properties and actin architecture, providing a potential mechanism for the maturation of nascent adhesions into focal adhesions.
    DOI:  https://doi.org/10.1126/sciadv.aeb6691
  24. ACS Sens. 2026 May 06.
      Adenosine triphosphate (ATP) serves as the universal energy currency in cellular metabolism. However, real-time analysis of ATP dynamics in prokaryotes remains a challenge due to significant intracellular pH fluctuations and high background interference. To address this, we developed IGAS, a novel genetically encoded biosensor engineered by integrating a binding protein derived from Bacillus subtilis PS3 with the acid-resistant fluorescent protein cpmCherry and miRFP670nano3. Characterization revealed that IGAS exhibits a robust 2.8-fold dynamic range, high selectivity for ATP, and remarkable pH stability. When expressed in E. coli, IGAS enabled real-time monitoring of intracellular ATP fluctuations throughout the bacterial growth cycle, demonstrating high consistency with standard luciferase assays. Furthermore, guided by molecular dynamics (MD) simulations, we identified key residues to engineer IGAS variants with tunable affinities. These sensors were successfully applied to diverse cellular environments, ranging from cytoplasmic targeting to mammalian cell surface display. Collectively, our results demonstrate the excellent reversibility and versatility of IGAS, establishing it as a powerful tool for dynamic ATP detection in complex biological systems.
    Keywords:  ATP; FRET; fluorescence biosensor; live-cell monitoring; synthetic biology
    DOI:  https://doi.org/10.1021/acssensors.5c04623
  25. Sci Adv. 2026 May 08. 12(19): eaec1606
      Mechanical metamaterials with bistable elements can store vast amounts of information, but writing these memories requires impractical local control or lengthy multicycle protocols. We overcome this limitation with a dynamic control strategy that accesses any configuration in a single global drive cycle by leveraging the system's sensitivity to the drive and its time derivatives. We realize this strategy with bistable beams on a rotating platform, where drive cycles become orbits in a control space of angular velocity and acceleration. State changes occur when these orbits cross switching thresholds, which we rationally design so that each state can be accessed by a single drive orbit. We construct a five-bit system and demonstrate its full addressability by selecting drive orbits that write all 26 uppercase letters of the alphabet in ASCII representation. This dynamic control paradigm offers a general route toward smart, remotely operated devices across various physical domains.
    DOI:  https://doi.org/10.1126/sciadv.aec1606
  26. ACS Synth Biol. 2026 May 04.
      Selective encapsulation of target enzymes is an increasingly well-studied field, with a host of potential applications for biotechnology. Natively, many bacteria utilize bacterial microcompartments (BMCs) for enzyme encapsulation to enhance catalysis. BMCs are protein shells that enable selective localization of targeted metabolic enzymes and may improve catalytic rates by colocalizing pathway enzymes and/or serve to sequester toxic or volatile intermediates. The microcompartment shell of Haliangium ochraceum (HO) is a notable BMC chassis because of its modularity and versatility; it is easily expressed and assembled outside its native host and can accept a wide array of cargo. Recently, it was demonstrated that assembly of HO BMC shells can be easily achieved in vitro. Following up on our previous work on in vivo assembly of HO-BMCs with triose phosphate isomerase (TPI) as a model enzyme cargo, here we have demonstrated the advantages of in vitro assembly (IVA) for targeted enzyme encapsulation. We achieved variable loading of BMC shells with targeted amounts of TPI and demonstrated enhanced thermal stability of encapsulated TPI versus free TPI up to 62 °C.
    Keywords:  bacterial microcompartments; catalysis; enzymes; protein crowding; synthetic biology; thermal stability
    DOI:  https://doi.org/10.1021/acssynbio.6c00074
  27. Proc Natl Acad Sci U S A. 2026 May 12. 123(19): e2535888123
      Many protein low-complexity domains (LCDs) self-associate to enable cellular function, yet fundamental questions remain regarding how polypeptide chemical and structural features beyond side chain identity contribute to LCD-LCD interactions. For instance, the folds adopted by globular proteins emerge from constraints enforced by homochirality of genetically encoded polypeptides. However, it remains unclear to what extent similar geometric constraints apply to LCD self-association. Herein, we use protein total and semi-synthesis to probe the contribution of Cα stereochemistry to LCD self-association with synthetic Chiral Inversion Mutagenesis (ChIM). By introducing targeted L-to-D amino acid inversions, ChIM identifies Cα stereocenters under geometric constraint without modification of side-chain functionalities. We apply ChIM to the LCDs of inner nuclear lamina protein Emerin and neurofilament light chain and find that chiral inversion produces strongly position-dependent effects upon LCD self-association. Our study describes essential structural features that enable LCD self-association and chemical strategies to interrogate LCD biochemistry.
    Keywords:  chiral inversion mutagenesis; low-complexity domains; protein oligomerization; protein self-association; synthetic protein chemistry
    DOI:  https://doi.org/10.1073/pnas.2535888123
  28. Nat Commun. 2026 May 06.
      Wearable chemical microreactors are highly desirable for life-sustaining processes such as on-demand oxygen-generation, but their development has been hindered by the lack of materials that combine dynamic robustness, textile integrability, and ultra-efficient fluid transport. Herein, we show a wearable microreactor based on armored aramid aerogel hollow fibers. Reinforcing these fibers with heat-shrink tubing yields textile-compliant elasticity while preserving their nanoporous structure. Subsequently, infusing a low-surface-energy liquid into the mesopores of aerogel walls creates a nanoconfined lubricant layer that reduces microfluidic drag by up to 68.1% compared to solid-walled channels. Finally, a O2-generated wearable microreactor prototype (268 g) achieves high space-time yield, 100% oxygen purity, and maintaining oxygen-supply under physical stress. In vivo trials at 4998 meters altitude demonstrate rapid blood oxygen saturation recovery, effectively alleviating acute hypoxia. This work establishes a materials paradigm that overcomes the trade-off between wearability and continuous-flow microreactor in on-body chemical synthesis.
    DOI:  https://doi.org/10.1038/s41467-026-72772-3
  29. Angew Chem Int Ed Engl. 2026 May 05. e20600
      Scalable genetic circuits are essential for implementing complex functions in living cells. Toward this goal, RNA regulators can provide a much-needed parts library with added benefits of low metabolic load, design flexibility, and logic capacity. However, despite the great potential of synthetic RNA circuits, constructing such circuits with wide dynamic ranges and multiplexed regulatory cascades remains a challenge. To address this, we introduce RATEX (Ribosome-Assisted Transcriptional EXpression controller) by integrating a translation-to-transcription converter with synthetic RNA regulators, enabling a compact and scalable RNA-programmed circuit architecture. The RATEX platform repurposes a large library of well-characterized translation regulators with up to 1,492-fold gene regulation, while leveraging natural ribosome-mediated sensing of diverse environmental inputs, such as metabolites. We demonstrated multi-input logic processing with up to a 6-input OR logic gate for RNA inputs and hybrid 3-input logic gates to sense diverse metabolite and small-molecule inputs alongside RNA signals. Signal amplification with multiplexed combinatorial control of RNA outputs was achieved through multiplexed signaling cascades. Finally, the RNA- and metabolite-sensing 3-input AND gates were used to control cellular morphology and intracellular spatial organization. Together, the RATEX platform, with its scalable and modular architecture, offers a broad potential design space for synthetic biology and biotechnology.
    Keywords:  RNA; cellular programming; logic gate; ribosome‐mediated transcription regulation; synthetic biology
    DOI:  https://doi.org/10.1002/anie.202520600
  30. Nature. 2026 May;653(8113): S1-S3
      
    Keywords:  Cell biology; Genetics; Policy; Sustainability; Synthetic biology
    DOI:  https://doi.org/10.1038/d41586-026-01420-z
  31. Matter. 2026 Apr 01. pii: 102669. [Epub ahead of print]9(4):
      Biological systems, including proteins, employ water-mediated supramolecular interactions to adopt specific conformations to support their functions. Here, we present dynamic porous crystals of aliphatic dipeptides with sequence-isomers of variable conformational entropy (leucine (L) and isoleucine (I)) exhibiting shallow-energy landscapes, with various reconfigurable topologies and consequent mechanics accessible through changes in relative humidity and temperature. Specifically, for LI crystals, changes in water chemical potential cause the solid-state porous architecture to reorganize and reversibly transition between perpendicular and parallel honeycomb structures, as well as layered van der Waals structures, leading to significant and distinct variations in macroscopic morphologies, mechanical properties, and photophysical properties. These dynamic crystals are achieved by leveraging non-directional side-chain interactions with confined water, which drive the phase transition while stabilizing the structures. Our findings highlight the potential of minimalistic peptide designs, inspired by protein architecture, to create dynamic solid-state materials that adjust their properties in response to environmental stimuli.
    Keywords:  Leu-Ileu; Peptide crystals; aliphatic side-chain interactions; hydrates; mechanical properties; nanoconfined water; phase transition; photophysical properties; porous materials; reconfigurable structures
    DOI:  https://doi.org/10.1016/j.matt.2026.102669
  32. Mater Today Bio. 2026 Jun;38 103143
      Variable-stiffness materials are engineered systems that can reversibly tune their mechanical stiffness through diverse mechanisms. In recent years, researchers have paid growing attention to these materials because they can adapt to different tasks, support multiple functions, and safely interact with soft biological tissues. For these reasons, they show strong potential for biomedical devices. However, most existing studies focus on single material systems or individual actuation modes, which limits the integration of different stiffness-control strategies within metamaterial-inspired architectures. As a result, cross-mechanism synergy remains underexplored, and unified system-level design rules are still lacking. This review summarizes recent progress in variable-stiffness materials for biomedical devices over the past decade. We divide current approaches into three main groups based on their working mechanisms: jamming-based systems, stimuli-responsive material-based systems, and antagonistic actuation-based systems. For each group, we explain the basic working principles and typical structural designs. We then describe how different activation methods control stiffness and support functional adaptation. Building on this, an application-oriented analysis is conducted across five representative biomedical device domains, including drug delivery systems, wearable assistive devices, minimally invasive surgical tools, bone repair applications, and adaptive sensing platforms, with a comparative evaluation of the suitability and prevalence of different stiffness modulation mechanisms in each domain. Finally, we discuss future research directions. These include AI-based real-time stiffness control, multimodal human-machine interfaces, 4D-printed adaptive structures, and bio-integrated hybrid materials. Together, these advances may help move Variable-stiffness materials from laboratory studies toward practical clinical use.
    Keywords:  Adaptive stiffness; Biomechanical modulation; Compliance matching; Mechanotransduction; Stimuli-responsive materials
    DOI:  https://doi.org/10.1016/j.mtbio.2026.103143
  33. Mater Today Bio. 2026 Jun;38 103133
      Though extracellular vesicles (EVs) contain much of the cellular machinery required for actively remodeling extracellular matrix (ECM), they are mostly appreciated for their roles in reprogramming cell proxies. Using a bottom-up biomimetic system, we show that breast cancer cell-derived EVs at the nanoscale can play an active role in collagen I matrix formation at the microscale. EVs nucleate new fibrils, recruiting collagen molecules from solution and enhancing fibril growth and network formation, resulting in more densely packed matrices with significantly increased storage and loss moduli. These effects are specific to EV membrane composition and cannot be reproduced using trypsinized EVs, synthetic liposomes, or mechanically extruded plasma membrane material. EVs become integrated into the fibril structures that they help form, reminiscent of matrix vesicles found within tissues. This represents a plausible way by which EVs are deposited into the ECM, becoming signaling cues for resident cells.
    Keywords:  Bottom-up synthetic biology; Cancer; Extracellular matrix; Extracellular vesicles; Soft matter mechanics
    DOI:  https://doi.org/10.1016/j.mtbio.2026.103133
  34. Sci Adv. 2026 May 08. 12(19): eaed0994
      Controlling collective behavior in the microscale is essential for advancing autonomous robotic systems in complex environments. While biohybrid microrobotic swarms offer considerable promise for targeted therapeutic and remediation applications, their programmable assembly and collective behavior remain challenging. Here, we describe an attractive light-triggered approach for enabling reconfigurable swarming of biohybrid microrobots based on the green microalga Chlamydomonas reinhardtii (CR). Such reversible swarming behavior is realized by combining the wavelength-dependent assembly ability of CR and its inherent phototactic properties with light exposures through a series of different mask openings that define the desired swarm geometry. Changes in the projected light enable dynamic modulation of the swarm shape and size, including real-time swarm splitting and merging behaviors. The concept was explored toward artificial intelligence-assisted wound targeting applications through the creation of microrobot swarms customized to exposed wound areas. Such powerful swarming capabilities offer considerable promise for the collective behavior of biohybrid microrobots toward important practical applications.
    DOI:  https://doi.org/10.1126/sciadv.aed0994
  35. ACS Appl Mater Interfaces. 2026 May 07.
      Bioelectrical cues are essential for cardiac function and regeneration, yet current electrostimulation strategies rely on invasive electrodes that limit spatial control and clinical translation. Here, we report magnetoelectric nanocomposite hydrogels that combine core-shell CoFe2O4@BiFeO3 magnetoelectric nanoparticles (ME NPs) with a photo-cross-linked methacrylated gelatin (GelMA) network, enabling wireless electroactivity through externally applied magnetic fields within a soft, biomimetic three-dimensional scaffold. Structural and physicochemical analyses confirmed the successful synthesis of crystalline core-shell ME NPs with strong interfacial coupling, as demonstrated by transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and magnetic hysteresis measurements showing exchange bias effects. Homogeneous incorporation of ME NPs within GelMA produced highly porous and interconnected hydrogels, as revealed by scanning electron microscopy and microcomputed tomography. The presence of nanoparticles reduced equilibrium swelling and refined pore architecture, suggesting increased effective cross-linking density and nanoparticle-polymer interactions. Mechanical testing showed soft elastomeric behavior with compressive moduli compatible with cardiac tissue. Under dynamic magnetic stimulation, magnetoelectric hydrogels significantly enhanced cardiac cell viability, proliferation, and morphological organization compared with pristine GelMA controls. After 10 days, the metabolic activity of cells cultured on GelMA-ME NP hydrogels under stimulation was approximately 3-fold higher than that of unstimulated GelMA. These results demonstrate that magnetoelectric hydrogels provide an effective platform for wireless electrostimulation, offering promising opportunities for cardiac tissue engineering and implantable bioelectronic therapies without wired electrodes.
    Keywords:  GelMA hydrogels; cardiac tissue engineering; core−shell nanoparticles; magnetoelectric nanocomposites; wireless electrostimulation
    DOI:  https://doi.org/10.1021/acsami.6c05467
  36. Nat Chem. 2026 May 06.
      Aptamers are a versatile alternative to antibodies as they are smaller, easier to synthesize and less immunogenic. However, while antibodies are composed of 20 chemically diverse amino acids and are established therapeutics, aptamers are composed of only 4 similar nucleobases, thereby limiting their therapeutic potential. Aptamer chemical modifications are restricted to maintain compatibility with enzymatic selection. Here we introduce aptamer-like encoded oligomers (alenomers), highly chemically modified aptamers that are read and sequenced using a DNA code branching from and corresponding to the target-binding oligomer. We build ~300,000-member DNA-encoded libraries using an automated DNA synthesizer and split-and-pool methods, and screen them for protein binding via next-generation sequencing. In contrast to aptamers, alenomers are not restricted by the need for conservative enzyme-compatible modifications. They can thus explore an almost limitless chemical space, enabling the discovery of highly stable, high-affinity protein-binding aptamers, while offering structural insights into their interactions with target molecules.
    DOI:  https://doi.org/10.1038/s41557-026-02099-5
  37. Science. 2026 May 07. 392(6798): 582-583
      Engineered enzymes enable kilogram-scale synthesis of drug for high-cholesterol conditions.
    DOI:  https://doi.org/10.1126/science.aeh1396
  38. bioRxiv. 2026 Apr 29. pii: 2026.04.26.720198. [Epub ahead of print]
      The extracellular matrix (ECM) is a highly dynamic network of proteins forming the structural organizer of all tissues. Different cell populations contribute to the assembly of the 150+ proteins of a functional ECM. In addition, different ECM subtypes, supporting distinct cellular functions, are found in every organ. Spatial transcriptomics (ST) provides a unique, yet untapped, opportunity to identify which cell populations contribute to ECM production with spatial context. Applied to healthy and diseased samples, this method can identify ECM changes that could be exploited for therapeutic purposes. Here, we introduce MatriSpace, a computational framework to mine ST datasets with a focus on ECM genes. MatriSpace offers two operating modes: researchers can either upload their own ST datasets or explore a large collection of public datasets. Upon analysis, MatriSpace returns spatially resolved maps of matrisome gene expression in relation to cell populations, at multiple levels: from single-gene analysis to tissue niches and functional ECM units. MatriSpace is available as an R package and an online Shiny App (https://matrinet.shinyapps.io/matrispace), making it accessible to all users regardless of their level of expertise.
    DOI:  https://doi.org/10.64898/2026.04.26.720198
  39. Trends Biotechnol. 2026 May 05. pii: S0167-7799(26)00142-3. [Epub ahead of print]
      Dynamic regulation of metabolic pathways is critical for optimizing microbial production, yet robust quorum-sensing (QS) systems remain largely unavailable in eukaryotic microorganisms. Here, we establish a bacterial-derived QS platform in Saccharomyces cerevisiae by repurposing the noncanonical RpaI/RpaR system (a LuxI/R-type QS system), which produces p-coumaroyl-homoserine lactone as a signal molecule, bypassing a fundamental metabolic barrier that has prevented functional bacterial QS in eukaryotes. The engineered circuit features low leakage, high sensitivity, and broad dynamic range. By coupling QS with signal amplification and clustered regularly interspaced short palindromic repeats (CRISPR) interference modules, we create a bifunctional cascade system enabling autonomous transcriptional activation and repression. This QS platform enables growth-production decoupling and improves the production of cordycepin, geraniol, and 3-hydroxypropionic acid in both baseline and high-producing strains. Our work establishes a functional bacterial QS system in yeast and expands the synthetic biology toolkit for eukaryotic hosts.
    Keywords:  RpaR/RpaI; bifunctional cascade circuits; dynamic regulation; quorum sensing; yeast
    DOI:  https://doi.org/10.1016/j.tibtech.2026.04.007