bims-enlima Biomed News
on Engineered living materials
Issue of 2026–09–20
27 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool



  1. Sci Adv. 2026 Sep 18. 12(38): eaeg9893
      Information processing through intrinsic physical processes in materials enables energy-efficient, bioinspired computing paradigms. In particular, mechanical transformations at the nanoscale stand out as a versatile and efficient mechanism for sensitive and highly tunable control. Here, we introduce an in-material computing platform leveraging the mechanical properties of nanoscale soft matter. Overcoming the limitations of conventional mechanical systems, our platform enables subnanometer control and engineered dynamics, which we demonstrate in an electromechanically tunable tunneling junction composed of a nanometer-thin poly(dimethylsiloxane) film. In this device, voltage-induced reconfigurations translate into a nonlinear, time-dependent electrical response. We use these temporal dynamics, arising from the viscoelastic memory of the polymer, to demonstrate an artificial neuron. As neural functionalities are embedded within the intrinsic material properties, energy efficiencies beyond those of biological systems are projected with much smaller active areas. Overall, our work establishes a design framework for extremely scaled mechanical tunability, opening emerging applications in energy-efficient, bioinspired computing, and intelligent materials and systems.
    DOI:  https://doi.org/10.1126/sciadv.aeg9893
  2. Mater Today Bio. 2026 Oct;40 103594
      Rotational molding (RM) is a widely used industrial process for producing hollow polymeric structures, yet it remains largely unexplored for biomaterials fabrication. Here, a low-cost 3D-printed biofabrication platform is introduced that adapts the general concept of RM to generate tunable hollow constructs with high structural fidelity. Using uniaxial RM, tubular-like hydrogels with precisely controlled diameter and wall thickness are generated by crosslinking light-responsive natural-based polymers, such as modified proteins and polysaccharides, under mild, cell-compatible conditions. The process yields reproductible geometries and well-defined walls while maintaining long-term cell viability. Furthermore, extending the system to biaxial RM allows the rapid, one-step fabrication of more complex hollow 3D architectures. By integrating established RM principles with biocompatible photochemistry, this accessible platform provides a scalable and versatile route to engineer hollow hydrogel architectures using virtually any kind of hydrogel forming material, independent of their rheological properties or crosslinking conditions. These capabilities expand opportunities in tissue modeling, biohybrid living actuators, and regenerative medicine, positioning RM as a powerful strategy for the controlled design of functional hollow hydrogels.
    Keywords:  Biofabrication; Hydrogels; Polysaccharides; Proteins; Rotational molding; Tissue engineering
    DOI:  https://doi.org/10.1016/j.mtbio.2026.103594
  3. Cell Biomater. 2026 Jul 21. pii: 100369. [Epub ahead of print]2(7):
      Engineered tissues could one day offer critical therapeutic relief for those requiring whole organ transplantation. Yet, their translation remains hindered by the need for robust vascularization throughout tissues of organ-scale sizes. Here, we used selective laser sintering of sacrificial isomalt templates to pattern vascular-promoting "tracks" across murine organ-scale tissue constructs. Upon implantation in mice, the patterned tracks architecturally guided host-mediated vascularization within fibrin and gelatin methacrylate/methacryloyl (GelMA) constructs. While the inclusion of tracks improved the vascularization response within both matrices, GelMA constructs demonstrated greater implant stability after 1 week in vivo. Subsequent implantation of GelMA constructs that were densely cellularized generated widespread, volumetric circulatory integration via both track-guided and self-assembled new blood vessels. This platform enables the generation of vascular networks spanning large, engineered tissues that can fully integrate with host circulation and represents a significant step toward the development of clinically translatable organ-scale tissues.
    Keywords:  Sacrificial templating; artificial tissue; engineered vasculature; vascularization
    DOI:  https://doi.org/10.1016/j.celbio.2026.100369
  4. Colloids Surf B Biointerfaces. 2026 Sep 08. pii: S0927-7765(26)00753-8. [Epub ahead of print]269 116165
      Protein-based hydrogels have emerged as a versatile class of biomaterials that combine the intrinsic biological functionality of proteins with the structural adaptability of hydrated three-dimensional networks. Their biocompatibility, bioactivity, and extracellular matrix-mimetic characteristics have attracted significant interest in tissue engineering, regenerative medicine, and drug delivery. Advances in protein engineering, synthetic biology, supramolecular chemistry, and biomolecular conjugation have enabled precise control over protein structure, intermolecular interactions, and network organization, transforming proteins into highly programmable building blocks for multifunctional hydrogel systems. This review summarizes the design principles of engineered protein hydrogels, emphasizing the roles of structural motifs, bioactive domains, and stimuli-responsive elements in regulating hydrogel assembly and functionality. Recent developments in physical and chemical crosslinking strategies are highlighted, together with their impacts on network architecture, mechanical performance, degradation behavior, and stimulus responsiveness. Particular attention is given to structure-property-function relationships linking protein design and assembly to hydrogel performance. These advances have facilitated the development of protein hydrogels for tissue regeneration, wound healing, therapeutic delivery, three-dimensional cell culture, and biofabrication, underscoring their promise as next-generation biomaterials.
    Keywords:  Biomedical applications; Crosslinking strategies; Protein engineering; Protein hydrogels; Regenerative medicine
    DOI:  https://doi.org/10.1016/j.colsurfb.2026.116165
  5. Biofabrication. 2026 Sep 18.
      Three-dimensional (3D) printing of hydrogels has advanced rapidly across numerous disciplines, including tissue engineering, medical devices, and biotechnology, enabling applications including cell scaffolds, drug delivery systems, and biosensors. However, the rapid fabrication of multi-layered complex hydrogel structures remains a significant challenge when employing traditional 3D printing methods. In this study, we demonstrated a four-dimensional printing (4D) approach that leveraged the shape-morphing properties of multi-layered hydrogels to efficiently create complex and fine featured structures using a digital projection stereolithographic printer. We optimized various poly(ethylene glycol) (PEG)-thiol-ene resin formulations and printing parameters to develop seven 3D printable resins that exhibited a wide range of volumetric swelling ratios, from 1.21 to 10.75, and a corresponding decrease in Young's modulus, from 98.10 kPa to 0.35 kPa. By varying the combinations of hydrogel layers with distinct swelling ratios and Young's moduli in the printed bilayer constructs, we could create curved structures with controllable bending angles ranging from 139° to 479° upon immersion in phosphate-buffered saline (PBS). We further demonstrated that the bending angles of these bilayer structures could be predicted using Timoshenko beam equation for lower-to-moderate swelling mismatch systems, while higher-swelling mismatch systems exhibited larger prediction deviations. By spatially patterning these resins within flat, multi-layered prints, we achieved programmed actuation into complex, doubly curved geometries such as domes and saddles. Furthermore, our approach enabled the fabrication of complex, nature-inspired curvilinear structures such as flowers, octopuses, and butterflies. This shape-morphing hydrogel printing method significantly reduces fabrication time, eliminates the need for structural supports, and maintains high precision and reproducibility. Overall, our technique offers a rapid and versatile strategy for producing small-scale, complex, multi-layered hydrogel structures, reducing print time from over an hour to just minutes. This approach shows potential utility in future bioengineering and soft robotics applications.
    Keywords:  4D printing; DLP; PEG-thiol-ene; multimaterial printing
    DOI:  https://doi.org/10.1088/1758-5090/aea9cd
  6. Nat Commun. 2026 Aug 20. pii: 9961. [Epub ahead of print]17(1):
      Precise control of surface patterns in assembled nanostructures remains a significant challenge in materials science. Here, we introduce a scalable bottom-up strategy utilizing living crystallization-driven self-assembly (CDSA) to fabricate tunable 3D surface patterns on polymer platelets. Inspired by biological growth increments, our approach leverages temperature-regulated, time-dependent crystallization to direct nanoscale organization, mimicking how nature constructs layered architectures. By exploiting polymer systems with temperature-dependent crystallization kinetics, we achieved diverse morphologies-including layered, concave, and convex features through controlled co-assembly and kinetic self-sorting. Temporal-thermal modulation was implemented in a continuous flow reactor, where precisely programmed residence times and temperature profiles enabled spatially resolved material deposition and growth history encoded in tree-ring-like patterns - control that is challenging or impossible to achieve using conventional batch methods. These features achieved lateral and vertical resolutions of ~73 nm and ~2 nm, respectively, allowing quantitative determination of directional crystallization rates (22.8 nm/s along the long axis and 13.4 nm/s along the short axis). Furthermore, modulating the number of layers provided a practical means to tune surface wettability. Our bioinspired design framework bridges synthetic self-assembly and natural structural logic, expanding opportunities for programmable materials in nanotechnology and functional systems.
    DOI:  https://doi.org/10.1038/s41467-026-76483-7
  7. Cell Biomater. 2026 Jul 03. pii: 100515. [Epub ahead of print]
      Patient-derived intestinal enteroids are valuable models for studying gastrointestinal physiology and disease, but their dependence on Matrigel™ limits reproducibility and clinical translation. Here, we developed a fully synthetic poly(ethylene glycol)-4-maleimide (PEG-4MAL) hydrogel platform to support human intestinal enteroid culture. Guided by enteroid transcriptomics revealing high expression of α2β1 integrin and matrix metalloproteinases, we systematically evaluated collagen-mimetic GFOGER and fibronectin-derived RGD (Arg-Gly-Asp) peptides combined with four MMP-sensitive crosslinkers. GFOGER-functionalized hydrogels significantly outperformed RGD formulations across all metrics. The optimized PEG-4MAL-GFOGER formulation demonstrated enteroid formation efficiency and viability approaching Matrigel™ performance. Bulk RNA-sequencing across multiple patient-derived lines demonstrated transcriptomic similarity between synthetic and Matrigel™ hydrogels, with preservation of stem cell, differentiation, and regional identity markers. This rationally designed synthetic platform overcomes key limitations of biological matrices while supporting robust enteroid growth and functionality comparable to standard biological matrices.
    Keywords:  cell adhesive peptides; intestinal organoids; matrix metalloproteinase-sensitive crosslinkers; synthetic hydrogels
    DOI:  https://doi.org/10.1016/j.celbio.2026.100515
  8. Proc Natl Acad Sci U S A. 2026 Sep 22. 123(38): e2603322123
      Despite extensive research on advanced soft materials, how fracture resistance evolves under dynamic loading and how cracks propagate remain incompletely understood. Here we show that dynamic fracture in long-chain, highly entangled polymer hydrogel networks with near-perfect elasticity is governed by localized viscous dissipation at the crack tip. Using highly entangled gels as a model system, we systematically vary network and loading parameters to evaluate the effects of loading rate, network topology, and solvent viscosity on fracture behavior. We find that, due to viscoelastic dissipation, the dynamic fracture toughness can be significantly lower than the quasi-static fracture toughness. Cracks can propagate at velocities approaching the shear-wave speed and undergo pronounced, unconventional branching. We develop a shear-lag model to describe the dissipation mechanism. The model predicts that the fracture energy scales inversely with a Weissenberg-like number ([Formula: see text]) that combines strain rate, chain length, mesh size, and solvent viscosity, and it recovers the Lake-Thomas limit at low values of [Formula: see text]. These results reveal how localized viscous dissipation governs fracture in highly elastic, entangled hydrogels and provide design principles for improving failure resistance in soft materials and devices operating under dynamic loading.
    Keywords:  crack branch; dynamic fracture; highly entangled networks; hydrogel viscoelasticity; rate-dependent dissipation
    DOI:  https://doi.org/10.1073/pnas.2603322123
  9. Bioact Mater. 2027 Feb;68 82-95
      Antimicrobial resistance (AMR) represents an escalating global health crisis, demanding alternative strategies to reduce resistant pathogen burden across environments. Microbe-based biocontrol is promising, yet effectively deploying it in practical settings remains challenging. In this study, we present a 3D bioprinted core-shell construct featuring a polyethylene glycol diacrylate (PEGDA) shell with tunable nanoscale porosity, encapsulating germinable spores of the biocontrol agent Bacillus subtilis TH035. This configuration supports long-term spore viability while providing protection from common environmental stressors including UV-C irradiation, ethanol exposure, and desiccation over 4 weeks. The nanoporous PEGDA shell enables effective bacterial confinement while facilitating sufficient metabolite exchange for B. subtilis germination and growth, as well as suppression of methicillin-resistant Staphylococcus aureus (MRSA) growth by approximately one order of magnitude. This approach demonstrates the feasibility of embedding B. subtilis spores within engineered scaffolds for extended competitive functionality. The versatility and scalability of digital light processing (DLP) based bioprinting offers significant potential for tailored designs and high-throughput manufacturing. This proof-of-concept platform may find future applications in areas such as biomedical packaging, environmental sanitation, and built environment surface coatings, particularly in settings where intermittent moisture or nutrient availability can support spore germination and biocontrol activity.
    Keywords:  3D bioprinting; Antimicrobial resistance; Bacillus subtilis; Biocontrol; Engineered living materials; Hydrogels; MRSA; Pathogens
    DOI:  https://doi.org/10.1016/j.bioactmat.2026.08.025
  10. Macromol Rapid Commun. 2026 Sep 16. e70433
      Injectable hydrogels have been recognized as an important class of soft materials for many enticing applications, yet it remains a challenge to program functions in one hydrogel substrate. Here, we report on dynamic hydrogels bearing injectable capacity and modular functionalities enabled by hydrazone formation. The hydrogel is generated by (cis, cis)-cyclohexane-1, 3, 5-tricarbohydrazide (H) and aldehyde-decorated hyaluronic acid (HA-A) through hydrazone formation. Due to the intrinsic dynamic feature of hydrazone bonds, the hydrogels are capable of rapidly recovering against mechanical damage, which makes the hydrogels injectable. Importantly, the residual hydrazide groups in the hydrogel network allow for the incorporation of various molecular modules through hydrazone formation, enabling the hydrogels to have a variety of chemical functions. Moreover, relying on a hydrazone formation-based self-assembly system, we are even able to incorporate supramolecular nanofibers into the hydrogel network. The incorporation of supramolecular nanofibers increasing the plateau storage modulus from approximately 200 to 20 000 Pa and the yield strain from 180% to 360%, while preserving the injectable behavior. This work offers a simple approach for the development of injectable hydrogels with tunable functions for diverse applications such as drug delivery, tissue regeneration, and machine-human interfaces.
    Keywords:  dynamic covalent chemistry; injectable hydrogels; self‐assembly; self‐healing; supramolecular chemistry
    DOI:  https://doi.org/10.1002/marc.70433
  11. Cell Biomater. 2026 Jun 09. pii: 100498. [Epub ahead of print]
      Recent advances in hydrogel design and mechanobiology have underscored the importance of extracellular matrix mechanical cues in guiding cell fates in 3D. However, most studies focus on bulk mechanical properties, which can differ markedly from the microscale mechanical cues that cells experience. Within a 3D hydrogel network, cells actively exert forces to push, pull, and remodel their immediate surroundings. Increasing evidence suggests that these local mechanical properties are dominant regulators of cell fates. This review summarizes recent advances in hydrogel engineering strategies, including crosslinking mechanisms and polymer architectures, that offer control over microscale matrix mechanics at the cellular scale. It synthesizes current understanding of how microscale mechanical cues modulate biological outcomes in 3D, spanning regenerative medicine and disease progression. Key techniques for measuring microscale mechanics and associated outstanding technical challenges are discussed. Finally, future directions for defining the mechanisms linking local hydrogel mechanics to long-term biological outcomes are discussed.
    Keywords:  Cell fates; Hydrogels; Mechanics; Mechanobiology; Microscale; Regenerative medicine; disease modelling
    DOI:  https://doi.org/10.1016/j.celbio.2026.100498
  12. Proc Natl Acad Sci U S A. 2026 Sep 22. 123(38): e2613575123
      Patterns in soft solids play essential roles across many fields and are created through diverse strategies. Here, we study the complex three-dimensional (3D) patterns which emerge directly from the fractured surfaces of soft stretchable materials. Using polyacrylamide hydrogels as model materials, we investigate the patterns on fractured gels with various crosslinker concentrations. In these systems, the crack front grows with 3D discontinuities that leave distinct step-like traces on the main fracture plane. We characterize the morphology using two geometric parameters: the step height t and step angle θ, which are highly related to material properties as shown by experiments and modelings. We find that for soft stretchable materials, the step height is on the order of the fractocohesive length Rf, rather than the previously claimed elastoadhesive length le. The step angle increases with network crosslinker concentration and approaches a plateau of magic ~45° at high crosslink densities. This work shows how nonlinear elasticity and fracture energy shape 3D fracture surface topography in soft materials and provides principles for designing functional patterned surfaces with tunable properties.
    Keywords:  elastoadhesive length; fractocohesive length; fracture pattern; step angle; step height
    DOI:  https://doi.org/10.1073/pnas.2613575123
  13. Nat Commun. 2026 Aug 20. pii: 9945. [Epub ahead of print]17(1):
      Recent advances in de novo protein design have greatly outpaced standard protein biochemistry workflows, making experimental validation a bottleneck. Here, we describe workflows to address the scale, speed and reproducibility of common in vitro protein testing methods, enabling at least an order of magnitude increase in throughput while reducing wetlab time. Semi-Automated Protein Production (SAPP) is a rapid, modular, scalable and cost-effective protocol, enabling up to milligram-scale protein production and standardized characterization - including yield, dispersity, and oligomeric state - of hundreds of designs per day, at the cost-equivalent of a few DNA oligos per construct. End-to-end protocol execution takes 48 hours, with ~6 hours spent benchside using standard laboratory equipment. We showcase the platform by rapidly screening redesigned fluorescent proteins, as well as identifying de novo binders that potently neutralize respiratory syncytial virus. We also developed a barcoding and demultiplexing protocol (DMX) to further reduce gene synthesis cost 5-fold by leveraging oligo pools as input DNA for the generation of thousands of sequence-verified arrayed clones. These protocols which combine optimized molecular biology, automated analysis, and optional open-source robotics should be widely adoptable, accelerating protein design.
    DOI:  https://doi.org/10.1038/s41467-026-76740-9
  14. Sci Adv. 2026 Sep 18. 12(38): eaeg3937
      Thin-walled structures capable of large, reversible deformation are key to multistability, origami, kirigami, and soft robotics. However, conventional fabrication techniques-including 3D printing, casting, and laser cutting-suffer from low durability, complex workflows, and restricted geometric freedom, hindering repeatable production. We introduce additive manufacturing-facilitated blow molding (AM-BM), combining the design flexibility of additive manufacturing with the robustness of blow molding. Replacing metal molds with additively manufactured resin ones enables rapid, low-cost fabrication of thin-walled components with tunable geometry and controllable wall thickness out of diverse thermoplastics. The thickness control allows thin-walled components to function as rigid load-bearing elements or compliant hinges. Demonstrations include multistable structures with geometry-controlled reconfigurability; origami and kirigami structures with extensive design freedom and uniform mechanical properties; and soft actuators and robots with ultrahigh load-to-weight ratios and rapid response. AM-BM offers a versatile, scalable route to thin-walled structures combining geometric freedom, mechanical functionality, and efficient production.
    DOI:  https://doi.org/10.1126/sciadv.aeg3937
  15. Cell Biomater. 2026 Sep 15. pii: 100405. [Epub ahead of print]2(9):
      Investigations into cardiac biology and drug discovery benefit from in vitro models that replicate human cardiac physiology. Current engineered heart tissue (EHT) models recapitulate aspects of this physiology but are limited by scalability, cost, and reproducibility. We report a one-step method to fabricate hydrogel molds using digital light processing (DLP) 3D printing to support EHT formation from human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). DLP enables rapid tuning of mold size, aspect ratio, and stiffness, while increasing scalability for high-throughput experiments without compromising EHT quality. DLP-fabricated EHTs show aligned extracellular matrix and display improvements in maturity versus 2D cultures, including a shift to fatty acid metabolism, increased myofilament density, and improved sarcomere organization. These EHTs also display expected responses to pathological stimuli (e.g., adrenergic agonism, increased stiffness), enabling disease modeling applications. Overall, 3D DLP-printed EHT molds provide versatile, scalable cardiac tissue platforms for both mechanistic studies and large-scale drug screening.
    DOI:  https://doi.org/10.1016/j.celbio.2026.100405
  16. Sci Adv. 2026 Sep 18. 12(38): eaek5988
      Methane-producing microbes use iron-sulfur cofactors as a nanowire to split electron energy through specialized megacomplexes. Understanding this process could enable more efficient methane production.
    DOI:  https://doi.org/10.1126/sciadv.aek5988
  17. Biomacromolecules. 2026 Sep 14. 27(9): 6096-6110
      Tissue engineering seeks effective strategies to integrate cells into scaffolds while preserving spatial organization and stability. Conventional approaches based on extracellular matrix molecules or adhesion peptides often provide weak and nonspecific attachments, limiting robust assembly of complex cellular architectures. Here, we investigate biorthogonal click chemistry to address these limitations. By enabling covalent cell-biomaterial bonding through strain-promoted azide-alkyne cycloaddition (SPAAC), we achieved stable cell-scaffold integration. As a proof of concept, we engineered artificial Bands of Büngner-like scaffolds by functionalizing silk microfibers with cyclooctyne groups and metabolically engineering Schwann cells to present azide functionalities. Over 15 days in vitro, these biohybrid scaffolds supported directed neurite outgrowth, preserved metabolic activity, and increased nerve growth factor levels at early time points. Our results support click chemistry as a robust strategy for assembling stable cell-laden scaffolds while preserving biological function, potentially enabling the tailored design of complex cellular architectures and microenvironments for tissue engineering applications.
    DOI:  https://doi.org/10.1021/acs.biomac.6c01009
  18. Nature. 2026 Sep;657(8132): 646-652
      Computers, like life, are usually out of equilibrium1,2. Undesired error states are thwarted by energetically costly kinetic control processes: proofreading of biological polymers, error correction in computing and redundancy in molecular programming. Unlike life as we know it, theory shows that computation can be embedded in a system relaxing to a thermodynamically favoured equilibrium state3,4. Machine learning and search algorithms use this idea5,6, although executed on non-equilibrium architectures at enormous energy cost. Physically implementing thermodynamically favoured computation requires a programmable medium amenable to energy landscape engineering. Here we demonstrate a thermodynamically favoured Scaffolded DNA Computer (SDC) on 10 programs, including MULTIPLICATION-by-3, DIVISION-by-2, 8-bit PARITY-detection and ADDITION of 25-bit numbers-a 100-bit computation. SDC algorithms have simple experimental protocols, can be reused dozens of times and small instances run in under a minute. Mathematical, physical and computer science principles explain why the SDC is thermodynamically favoured, why it does not require error-correction or precise kinetic control, and how it is programmable and scalable. This work creates a new way to think about equilibrium computation in all manner of synthetic systems.
    DOI:  https://doi.org/10.1038/s41586-026-10996-5
  19. ACS Chem Biol. 2026 Sep 14.
      Over the past two decades, engineering efforts have yielded aminoacyl-tRNA synthetases (aaRSs) capable of charging diverse noncanonical amino acids (ncAAs). Here, we report an unexpected and exploitable activity of these engineered aaRSs. In the absence of their cognate tRNA, aaRSs can release the ncAA-AMP intermediate, which labels proximal proteins via covalent acylation. Multiple different aaRSs exhibit this behavior, enabling both self-labeling and trans-labeling of proteins with ncAAs in vitro and in living cells. When using bioorthogonal ncAAs, the resulting labeled proteins can be further functionalized through bioorthogonal conjugation with a fluorophore for visualization or biotin for enrichment. Although labeling by existing aaRSs is slow, we provide preliminary evidence that improved activity is possible through further engineering. Taken together, these results establish a new potential approach for proximity-based protein labeling, analogous to BioID and TurboID. Many aaRSs are available to charge diverse ncAAs, creating opportunities for multiplexed labeling; i.e., different aaRS/ncAA pairs used simultaneously to probe multiple spatially/temporally distinct microenvironments.
    DOI:  https://doi.org/10.1021/acschembio.6c00682
  20. Nat Rev Chem. 2026 Sep 11.
      Ionizable lipid nanoparticles have emerged as a potent non-viral delivery platform for nucleic acid therapeutics, achieving clinical breakthroughs ranging from the FDA-approved small interfering RNA therapeutic to mRNA vaccines against coronavirus disease 2019 and respiratory syncytial virus. Their success stems from the ability of ionizable lipids to remain neutral in physiological environments, yet protonate in acidic endosomes, enabling the efficient release of genetic cargo. Over the last several decades, their structures have evolved extensively through the application of combinatorial chemistry, rational design, incorporation of functional elements and, most recently, machine learning and artificial intelligence-guided strategies. These innovations have expanded ionizable lipids from passive carriers into multifunctional materials capable of organ-specific targeting, responsiveness, immunomodulation and theranostics. In this Review, we highlight the development, synthesis and structural evolution of ionizable lipids as well as their emerging on-demand design functionalities and next-generation biomedical applications. We provide insights into the challenges and gaps for translation, manufacturing and expansion of lipid nanoparticle-mediated nucleic acid therapeutics for precision RNA medicine.
    DOI:  https://doi.org/10.1038/s41570-026-00865-0
  21. Nature. 2026 Sep 16.
      
    Keywords:  Computer science; Machine learning; Publishing
    DOI:  https://doi.org/10.1038/d41586-026-02899-2
  22. ACS Appl Mater Interfaces. 2026 Sep 18.
      Intracellular RNA regulates diverse cellular processes and represents an attractive target for materials-based control of gene expression. Here, we report a sequence-engineered DNA capsule platform that couples RNA recognition to programmable cargo release. The capsules are assembled via layer-by-layer hybridization of designed DNA strands onto calcium carbonate (CaCO3) templates, forming a hollow DNA shell in which antisense oligonucleotides (ASOs) function as both regulatory modules and molecular triggers. Upon hybridization with complementary target sequences, toehold-mediated strand displacement (TMSD) converts sequence recognition into controlled payload release while concurrently modulating transcript levels. Two capsule variants targeting MYH9 and p21 were constructed as model systems. Using DNA analog target sequences, the capsules showed concentration-dependent and sequence-selective responses with limits of detection of 16.7 nM and 7.9 nM for MYH9 and p21, respectively. Importantly, MYH9 RNA also triggered concentration-dependent tetramethylrhodamine-dextran (TMR-D) release, with a limit of detection of 14.0 nM, supporting the RNA-responsive nature of the capsule design. Cell-based experiments showed cell-associated fluorescence signals and sequence-dependent changes in migration and viability. Co-encapsulation of doxorubicin-modified dextran (DOX-D) further reduced cell viability relative to unloaded capsules. These results demonstrate a proof-of-concept nucleic acid material in which sequence-level design governs stability, RNA responsiveness, and triggered release behavior. This DNA capsule platform provides a modular framework for RNA-responsive biomaterial design and for integrating sensing and functional outputs at the cellular level.
    Keywords:  RNA sensing; antisense oligonucleotides; controlled release; layer-by-layer assemblies; strand displacement reactions
    DOI:  https://doi.org/10.1021/acsami.6c14993
  23. Nat Methods. 2026 Sep 11.
      The robustness and broad applicability of an optogenetic tool depends heavily on the properties of the underlying photoreceptor protein and its cognate binding partner-the light-responsive 'core'. Current red light optogenetic systems for mammalian cells rely on phytochrome-based photoreceptors: large (70-kDa) proteins that act as dimers, enforcing dimerization on attached proteins. Naturally occurring or engineered binding partners can function effectively, but large size, complex interaction, background binding, weak affinity and modest dynamic range remain limiting. Here we developed a small (17-kDa) monomeric biliverdin-binding photoreceptor, FenixS, and a highly selective, high-affinity binder, Ash1 (6 kDa) using structure-based design and directed evolution. Negligible OFF-state binding and a >1,200-fold increase in binding affinity upon 700-nm illumination yield a high-performance, ultralow background core for diverse applications. A FenixS-Ash1-based optogenetic tool for red light activation of transcription in mammalian cells performs robustly without biliverdin supplementation, with head-to-head comparisons confirming its control of gene expression versus established tools.
    DOI:  https://doi.org/10.1038/s41592-026-03223-6
  24. Nature. 2026 Sep;657(8132): 587-589
      
    Keywords:  Cell biology; Evolution; Microbiology
    DOI:  https://doi.org/10.1038/d41586-026-02849-y
  25. Nat Biotechnol. 2026 Sep 14.
      Simultaneous characterization of proteins, RNAs and glycans with a nanopore remains a substantial challenge. To advance toward this goal, we introduce a multifunctional adaptor, maleimido-C2-formylphenylboronic acid (maleimido-C2-FPBA), into the Mycobacterium smegmatis porin A (MspA) nanopore at the pore constriction site. Here we demonstrate that the engineered nanopore, MspA-FPBA, enables the simultaneous identification of a diverse set of analytes, including 21 proteinogenic amino acids, three post-translationally modified (PTM) amino acids, four canonical nucleoside monophosphates (NMPs), three epigenetically modified NMPs, four monosaccharides and five peptides. Combined with machine learning, this sensor achieves an overall accuracy of 98.7%. Furthermore, it generates predictable event signatures for specific analyte types, enabling the machine learning model to identify analytes without strictly relying on prearchived event features, as demonstrated by the nanopore analysis of yeast cell extract. Lastly, we apply MspA-FPBA for compositional analysis of G2 glycopeptides. Future integration of hydrolase with MspA-FPBA may further improve MspA-FPBA utility as a single system to identify diverse biomolecules.
    DOI:  https://doi.org/10.1038/s41587-026-03308-9
  26. Nat Commun. 2026 Aug 14. pii: 9774. [Epub ahead of print]17(1):
      To operate autonomously, minimal robot swarms must make timely and reliable collective decisions despite noisy individual sensing and severe constraints on communication, computation, and memory. Achieving this capability could expand their use in applications such as healthcare, disaster response, and environmental monitoring. Here, we study how such swarms can rapidly and reliably reach consensus on the best among n discrete options by comparing two canonical mechanisms of opinion dynamics-direct-switch and cross-inhibition-simple yet effective rules for collective information processing observed in biological systems across scales, from neural populations to insect colonies. We generalise existing mean-field models by incorporating asocial biases that influence opinion dynamics. While swarms using direct-switch reliably select the best option in the absence of asocial dynamics, their performance deteriorates when such biases are introduced, often leading to decision deadlocks. In contrast, bio-inspired cross-inhibition enables faster, more cohesive, robust, and scalable decisions across a wide range of biased conditions. Our findings provide theoretical and practical insights into the coordination of minimal swarms, with implications for a broad class of decentralised decision-making systems across biology and engineering.
    DOI:  https://doi.org/10.1038/s41467-026-76408-4