bims-enlima Biomed News
on Engineered living materials
Issue of 2026–08–23
35 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool
  1. Living circuit boards built by printing bacterial transistors.
  2. Discrete 2D Material Programming for 3D Shaping and Morphogenesis-Inspired 4D Bioprinting.
  3. Material agency: operationalizing the living/nonliving interface in engineered materials.
  4. Programmable biofunctionalization of bacterial cellulose via a dynamic co-culture platform.
  5. Self-Actuating 4D Cell-Strand Bioprinting.
  6. Nitrene generation and transfer for unnatural biosynthesis in living cells.
  7. Matrix stress relaxation drives glioblastoma cell response in viscoelastic biomaterials.
  8. Encapsulate bacteria in implantable hydrogels for living therapeutics.
  9. Soft Yet Tough Tanglemers Through Rapid Photopolymerization for DLP 3D Printing.
  10. Metastable Polymers for Circular 3D Printing.
  11. Engineering Multilayer Poly(ethylene glycol) Hydrogels via Off-Stoichiometry Thiol-Ene Chemistry.
  12. An insoluble de novo protein enables survival of Escherichia coli by sequestering a gene repressor.
  13. Automated synthetic cell-based screening for designed proteins with emergent functions.
  14. Genetic code expansion enables plant-directed control of bacterial activity.
  15. Hydraulic Pressure-Programmed Molecular Transport in Tough Hydrogels.
  16. Five ways 3D printing is improving lab work.
  17. Stress Transfer Within Microphase-Separated Structures: A Post-Synthetic Strategy to Impart Mechanoresponsiveness to Block Copolymer Materials.
  18. Evolutionary diversification via modular compliance for self-reconfigurable continuum robots.
  19. A diversified consortium of engineered biosensors enables multi-target quantification.
  20. Toward Long-Term Bioelectronic Interfaces: Mechanical Compliance Meets Immunocompatibility.
  21. A Protein Editing Method to Modify Proteins in Live Mammalian Cells.
  22. Morphogenesis of bacterial colonies in liquid crystalline environments.
  23. Facile Siderophore Assembly Enables Bacterial Delivery of Nucleic Acid Therapeutics.
  24. PANCS-Inhibitors: A rapid method to directly select for protein-protein interaction inhibitors.
  25. Surface-Engineered Poly(ethylene oxide)-Grafted Quantum Dot Inks for Green-Solvent-Processed Electroluminescent Devices.
  26. Beyond Stimuli Responsiveness: Toward Decision-Making Polymers.
  27. Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells.
  28. Next-Generation Glycan Materials Bridging Organic and Inorganic Chemistry.
  29. Tunable DNA-Stabilized Bicelles as Nanoscale Membrane Mimetic Systems.
  30. Tuning of Bacterial Cellulose Hydrogel Architecture during Fermentation through Polymer-Modified Growth Media.
  31. Partitioning law of polymer chains into flexible polymer networks.
  32. In vivo reconstruction of the cell lineage history of a developing mouse with DNA Typewriter, from zygote to late organogenesis.
  33. Massive-scale parallel gene synthesis with oligonucleotide hybridization.
  34. A Compact, Standalone & Battery-Powered 3D Organoid-on-Chip System with Programmable Flow Control.
  35. The HydroGym reinforcement learning platform for fluid dynamics.
  1. Nat Chem Biol. 2026 Aug 17.
    Living circuit boards built by printing bacterial transistors.
    Hamid Doosthosseini, Haorong Chen, Christopher A Voigt.
      The multicellular forms and functions seen in biology are controlled by cellular communication and collective computation. Reprogramming natural systems is difficult because they comprise many signaling molecules connecting a web of regulatory networks within cells. Here we apply principles from pass transistor logic (PTL) to design bacteria that can be easily reconfigured to perform computations on a solid surface. Strains of Pantoea agglomerans were built to encode two transistors (N-type and P-type) whose inputs and outputs are small molecules. They are connected by three relay strains that convert molecular diffusion to unidirectional flow. To build circuits, an acoustic liquid handler prints patterns of these five strains on a surface. By changing the pattern, not requiring any genetic changes, different operations are implemented, including multi-input multioutput logic, demultiplexor, half-adder and full-adder. This work demonstrates that only five cell types, each encoding a simple operation, can be scaled to create complex computational operations.
    DOI:  https://doi.org/10.1038/s41589-026-02300-3
  2. Adv Sci (Weinh). 2026 Aug 21. e77228
    Discrete 2D Material Programming for 3D Shaping and Morphogenesis-Inspired 4D Bioprinting.
    Fereshteh Family, Aneela Davuluri, Athulya Martin, Kyungsuk Yum.
      Programming in-plane growth in thin sheets enables 2-to-3D shape transformation into doubly curved morphologies common in living organisms. Despite its morphogenesis-inspired premise and intrinsic suitability for tissue-like systems, translating growth-programmed shaping into engineered living constructs remains challenging. Here, we report cell-compatible discrete 2D material programming for growth-driven 3D shaping and morphogenesis-inspired 4D bioprinting. By patterning cell-supportive microdomains within a responsive hydrogel matrix, we program in-plane growth to prescribe target metrics. This approach enables 4D bioprinting of living constructs that autonomously transform into prescribed 3D morphologies under physiological conditions. We establish design rules that expand the programmable 3D shape space, characterize time-dependent morphing dynamics, and demonstrate bioinspired motions. The transformed constructs maintain high cell viability and support tissue-relevant cellular behaviors. Cell-compatible discrete 2D material programming provides a platform for programmable morphogenesis and dynamic biofabrication, with potential relevance to hybrid living-synthetic systems, including bioinspired soft robotics, engineered tissue constructs, and cell-based devices.
    Keywords:  4D bioprinting; engineered living constructs; hydrogels; material programming; shape‐morphing materials
    DOI:  https://doi.org/10.1002/advs.77228
  3. Trends Biotechnol. 2026 Aug 18. pii: S0167-7799(26)00333-1. [Epub ahead of print]
    Material agency: operationalizing the living/nonliving interface in engineered materials.
    Andrea Belluati.
      The label 'engineered living materials' groups devitalized mycelium composites with metabolically active biosensors, applying shared metrics to systems with fundamentally different failure modes, safety profiles, and engineering requirements. This forum proposes a four-class operational taxonomy, a Maximum Agency Potential classification principle, and a minimum reporting standard that classify systems by biological agency dependence during use.
    Keywords:  biocontainment; biofabrication; biological agency; engineered living materials; operational taxonomy
    DOI:  https://doi.org/10.1016/j.tibtech.2026.07.036
  4. Trends Biotechnol. 2026 Aug 19. pii: S0167-7799(26)00331-8. [Epub ahead of print]
    Programmable biofunctionalization of bacterial cellulose via a dynamic co-culture platform.
    Fei Liu, Yanyi Wang, Bin Cui, Yanwen Feng, Jun Yue, Chao Zhong.
      Programmable biofunctionalization of bacterial cellulose (BC) is promising for constructing engineered living materials, but current microbial co-culture approaches struggle to combine coherent matrix formation, dynamic cultivation, and efficient matrix-associated protein functionalization. In this study, we report a polydopamine (PDA)-mediated, surface-immobilized dynamic co-culture platform that pairs Komagataeibacter rhaeticus for BC production with engineered Pichia pastoris for recombinant protein secretion. PDA-mediated co-immobilization preserves conformal BC growth under agitation while maintaining the functional partner near the forming matrix. Cellulose-binding-domain fusion further retains secreted protein cargoes within the BC network, enabling localized functionalization. The template-guided strategy supports geometry control, construct-size scaling, and incorporation of multiple engineered yeast populations. Modular genetic payloads enable pollutant degradation and enzymatic cascade-based analyte detection. As an application-relevant demonstration, lysostaphin-functionalized BC hydrogels effectively controlled Staphylococcus aureus infection and accelerated wound closure in a diabetic murine model. This work establishes a functionally extensible framework for bioactive BC-based living materials.
    Keywords:  bacterial cellulose; engineered living materials; in situ biofunctionalization; microbial co-culture; wound healing
    DOI:  https://doi.org/10.1016/j.tibtech.2026.07.032
  5. bioRxiv. 2026 Jul 28. pii: 2026.07.27.740975. [Epub ahead of print]
    Self-Actuating 4D Cell-Strand Bioprinting.
    Aixiang Ding, Ana F Cunha, Mariana B Oliveira, João F Mano, Eben Alsberg.
      Engineering biomimetic tissues with dynamically evolving 3D architectures represents an important direction for next-generation tissue engineering, as it enables recapitulation of the continuous morphogenesis of native tissues during development and regeneration. Here, a self-actuating 4D cell-strand bioprinting platform is developed to engineer complex tissue architectures through autonomous cell contractile force (CCF)-driven morphing without requiring external stimuli. The platform integrates a mechanically compliant and self-softening base hydrogel with embedded high-density cell strands printed using a fast-degrading carrier bioink. During culture, the carrier bioink rapidly degrades while the encapsulated cells proliferate and establish connected cellular networks, generating localized contraction that drives programmable shape transformation. Through spatial patterning of embedded cell strands, constructs with diverse morphologies, including V-shaped, helical, folded, and tubular architectures, are generated via controllable self-actuated morphogenesis. The platform further enables engineering of cartilage-like and bone-like tissues with well-defined curvature configurations and mechanically robust tissue matrices. In addition, programmable multi-tissue engineering is demonstrated through fabrication of a muscle-tendon junction-mimicking construct containing spatially organized fibroblast and myoblast compartments. This self-actuating 4D bioprinting strategy enables highly programmable and directionally controlled morphogenesis using a simple construct design with low cell amount requirements, providing a versatile platform for engineering dynamic tissue architectures.
    DOI:  https://doi.org/10.64898/2026.07.27.740975
  6. Nat Chem. 2026 Aug 18.
    Nitrene generation and transfer for unnatural biosynthesis in living cells.
    Isaac Donnell, Andrew Quest, Jeremy Tang, Maodun Zhang, Brandon Bloomer, Douglas S Clark, Aindrila Mukhopadhyay, John Hartwig, Jay D Keasling.
      Synthetic biology has enabled the production of natural and unnatural products from inexpensive sustainable feedstocks. Yet, the scope of available products has been limited largely to compounds accessible from nature's chemical reactions. Evolved enzymes can catalyse reactions of unnatural substrates or reactions not found in nature but often require the addition of synthetic reagents to purified enzymes or to resting cells containing those enzymes. Here we show that chemical reactions of metabolic intermediates produced intracellularly in living cells can include intermolecular nitrene transfers. The biosynthesis of N-acetoxyanilines, in combination with the generation and transfer of N-aryl nitrene intermediates from them catalysed by a cytochrome P450, generates amino alcohols, diamines, diarylamines and aminoalkyl arenes from simple carbon feedstocks. These products-common substructures of pharmaceuticals and agrochemicals-are challenging to synthesize by standard organic chemistry and were produced from inexpensive, renewable feedstocks. Evolution of the enzymes in this pathway showed that titres can be increased by engineering and that the products can be synthesized with high enantioselectivity.
    DOI:  https://doi.org/10.1038/s41557-026-02224-4
  7. Sci Adv. 2026 Aug 21. 12(34): eaef7087
    Matrix stress relaxation drives glioblastoma cell response in viscoelastic biomaterials.
    Sadegh Ghorbani, Michelle S Huang, Daiyao Zhang, Yueming Liu, Christopher Long, Riley Zwetsloot, Esther A T Mozipo, Rameshwar R Rao, Annika Enejder, Sarah C Heilshorn.
      The extracellular matrix (ECM) of glioblastoma (GBM) is known to modulate cell behavior, yet the specific contributions of matrix biochemical and biomechanical signaling remain poorly understood. To address this, we engineer a tunable hyaluronan-elastin-like protein (HELP) hydrogel to independently control ligand presentation and matrix viscoelasticity. Two peptides mimicking fibronectin (FBN) and tenascin-C (TNC) are incorporated into HELP along with hyaluronan, all of which are highly up-regulated in GBM. Using dynamic covalent chemistry, we develop hydrogels with matched stiffness but distinct stress relaxation profiles. Slow stress-relaxing matrices promote cell clustering and elevated expression of P-selectin, a GBM invasion marker. These matrices also result in increased nascent ECM production, increased lipid droplet storage, and altered cytokine secretion. Our results highlight the benefit of protein-engineered, viscoelastic biomaterials for modeling the tumor microenvironment and reveal matrix viscoelasticity as a critical regulator of GBM cell state, offering a tool for identifying previously unrecognized therapeutic targets.
    DOI:  https://doi.org/10.1126/sciadv.aef7087
  8. Matter. 2026 Aug 05. pii: 102962. [Epub ahead of print]9(8):
    Encapsulate bacteria in implantable hydrogels for living therapeutics.
    Rui Guo, Zhaoqi Duan, Ganghao Liang, Xiujun Fan, Jun Chen.
      Recent advances in implantable living materials have highlighted their potential for autonomous therapeutic delivery by integrating mechanically robust hydrogels with encapsulated therapeutic bacteria. By enabling long-term biocontainment, environmental sensing, and genetically programmed drug release within physiologically stable scaffolds, these living materials establish a versatile foundation for next-generation personalized therapeutics and closed-loop disease management.
    DOI:  https://doi.org/10.1016/j.matt.2026.102962
  9. Adv Mater. 2026 Aug 19. e74661
    Soft Yet Tough Tanglemers Through Rapid Photopolymerization for DLP 3D Printing.
    Yutong Liu, Tiffany N Jeng, Elizabeth A Recker, Ellen J Forehand, Gabriel E Sanoja, Zachariah A Page.
      Additive manufacturing of compliant materials that simultaneously combine softness, elasticity, and toughness remains a central challenge. Here, we report a single-resin photopolymerization strategy to produce densely entangled polymer networks ("tanglemers") via digital light processing (DLP) 3D printing using industrially abundant monomers. Comparisons between controlled and uncontrolled radical polymerizations reveal that the uncontrolled, free-radical approach at low initiator loadings and light intensities balances DLP-relevant gelation timescale with high molecular weight between crosslinks. The resulting elastomers and hydrogels exhibit a rare combination of properties, including low modulus (ET <1 MPa for elastomers and <100 kPa for hydrogels), high extensibility (εf > 400%), low hysteresis (∼10%), and high toughness (Ut > 1 MJ m- 3, Gc ≈ 1 kJ m- 2 for elastomers; Ut ≈ 1 MJ m- 3, Gc ≈ 3 kJ m- 2 for hydrogels). These materials translate from casting to DLP 3D printing with feature sizes down to ∼100 µm, surpassing commercial resins in softness and elasticity, while maintaining competitive toughness and aging resistance after initial accelerated weathering. This work establishes simple, single-resin formulations as a route to DLP-printable, defect-tolerant tanglemers with potential relevance to soft robotic, wearable, and biomedical technologies.
    Keywords:  3D printing; digital light processing; entanglement; photopolymerization; toughness
    DOI:  https://doi.org/10.1002/adma.74661
  10. Adv Mater. 2026 Aug 18. e74682
    Metastable Polymers for Circular 3D Printing.
    Johannes Markhart, Philipp Mainik, Eva Blasco.
      Reducing waste and enabling material reuse are central goals for sustainable advanced manufacturing. In light-based 3D printing, this requires moving beyond permanent networks toward systems that can be easily returned to their original molecular building blocks, while preserving good performance. Here, a shift toward metastable, 3D printable polymers is introduced, which are intrinsically programmed for controlled depolymerization under mild conditions, enabling circular recovery. This concept is realized using self-immolative polymers (SIPs), which undergo triggered, domino-like depolymerization upon activation of a specific labile unit. These polymers are formulated for high-resolution digital light processing 3D printing, yielding mechanically robust structures. Upon exposure to a defined trigger, the printed networks rapidly (in seconds) and completely disassemble under ambient conditions, regenerating their pristine monomers. These are recovered in near-quantitative yield and subsequently reprocessed into chemically identical printable polymers. This metastability-driven approach establishes a transformative pathway for circular 3D printing.
    Keywords:  3D printing; chemical circularity; digital light processing; metastable polymers; recycling; self‐immolative polymers
    DOI:  https://doi.org/10.1002/adma.74682
  11. ACS Appl Polym Mater. 2026 Aug 14. 8(15): 12772-12781
    Engineering Multilayer Poly(ethylene glycol) Hydrogels via Off-Stoichiometry Thiol-Ene Chemistry.
    Ridhi Pradhan, Ravinun Khamleart, Waqas Saleem, Michael J McShane.
      Multilayer hydrogels with spatially controllable mechanical and functional properties are increasingly valuable, yet their utility is often constrained by fabrication challenges such as weak interfacial adhesion as well as reliance on cytotoxic photoinitiators and UV exposure. This study presents a simple, robust, and photoinitiator-free method to engineer multilayer poly-(ethylene glycol) (PEG) hydrogels using off-stoichiometry thiol-ene (OSTE) Michael addition chemistry. By deliberately utilizing an alternating thiol-rich and vinyl sulfone-rich PEG formulation, residual functional groups are preserved at the layer interfaces and subsequently form covalent bonds between the adjacent layers, enabling strong interfacial adhesion without UV irradiation, photoinitiators, or adhesives. The resulting hydrogels exhibited rapid and tunable gelation (1-5 min), with mechanical properties spanning ∼0.5-6 kPa through varying polymer concentration (5-10 wt %) and thiol-ene ratio (0.6-1.6). Ellman's assay confirmed the presence of stoichiometry-dependent unreacted thiol groups, validating the proposed interfacial bonding mechanism. Peel tests revealed strong interfacial adhesion, with failure occurring within the bulk material rather than at the interface. Nanoindentation further revealed spatially defined stiffness profiles across the multilayer construct, confirming precise mechanical compartmentalization. The hydrogels displayed tunable swelling behavior and degradation profiles depending on the formulations. Additionally, all single- and multilayer hydrogels maintained high cytocompatibility (>90% NIH/3T3 mice fibroblast viability) independent of polymer concentration, thiol-ene ratios, or layering. Incorporation of alginate microparticles provided an additional strategy for modulating hydrogel properties, significantly reducing swelling and enhancing stiffness while preserving structural integrity. Overall, the findings established a platform for engineering heterogeneous hydrogel constructs with spatially controlled properties, biofunctionality, and compatibility features that make them relevant for biomedical applications.
    Keywords:  Michael addition; biomaterials; compartmentalization; interfacial adhesion; multilayer hydrogel; off-stoichiometry thiol–ene; spatially controlled mechanics
    DOI:  https://doi.org/10.1021/acsapm.6c01912
  12. Proc Natl Acad Sci U S A. 2026 Aug 25. 123(34): e2601204123
    An insoluble de novo protein enables survival of Escherichia coli by sequestering a gene repressor.
    Guanyu Liao, Sha Tao, Jessica L Dessau, Yejin Bann, Michael H Hecht.
      De novo proteins that share no ancestry with natural sequences can serve as additions to the evolved proteomes of living cells. Upon expression in cells, these novel proteins can provide biological functions that alter cell viability and growth. To isolate such proteins, we searched a combinatorial library of novel sequences by selecting for sequences that sustain the growth of Escherichia coli under conditions where the recipient cell would otherwise be inviable. This led to the identification of Resc4 (Rescuer 4), a de novo protein that sustains growth on minimal medium of an E. coli strain harboring a lethal deletion of metC, which encodes cystathionine [Formula: see text]-lyase, a conditionally essential enzyme in the biosynthesis of methionine. Surprisingly, despite its ability to rescue the deletion of a biosynthetic enzyme, Resc4 is insoluble. Nonetheless, Resc4 sustains the growth of [Formula: see text]metC cells by upregulating expression of metB, which encodes a different enzyme, cystathionine [Formula: see text]-synthase, which has a moonlighting activity that compensates for the deleted activity encoded by metC. Proteomic analysis revealed that Resc4 sequesters MetJ, the repressor of the methionine biosynthesis operon. Sequestration of MetJ leads to overproduction of cystathionine [Formula: see text]-synthase, thereby allowing it to rescue the deletion of metC. These results, taken together with previous findings on other de novo proteins, demonstrate that novel proteins added to a cell's proteome can perform life-sustaining functions, and may shed light on de novo gene birth-both in synthetic biology and in natural evolution.
    Keywords:  de novo gene birth; de novo proteins; metC; regulatory protein; synthetic biology
    DOI:  https://doi.org/10.1073/pnas.2601204123
  13. Nat Commun. 2026 Aug 15. pii: 8415. [Epub ahead of print]17(1):
    Automated synthetic cell-based screening for designed proteins with emergent functions.
    Kareem Al Nahas, Béla P Frohn, Aleksandra Šakanović, Frank Siedler, Petra Schwille.
      Designing minimal biological systems with emergent functions such as spatiotemporal self-organization is a central goal of bottom-up synthetic biology. While computational optimization and design show promise in accelerating functional protein engineering through Design-Build-Test-Learn cycles, screening libraries for complex functions remains a major challenge. Conventional screens typically lack the spatiotemporal resolution and cell-like confinement required in bottom-up synthetic biology. Here, we present PUREdrop, an automated microfluidic platform that encapsulates and expresses protein libraries in thousands of picoliter-sized synthetic cells per construct. PUREdrop distributes these across predefined wells of a 96-well plate for time-lapse imaging, enabling parallel quantification of expression kinetics and emergent functions. To demonstrate the platform's potential, we first screen computationally re-designed variants of the bacterial cell division protein FtsZ, and identify variants with altered bundling phenotypes and distinct kinetics. We then extend our screening procedure to general protein modulators of FtsZ and identify a combination that anchors filaments to the interface, producing a ring-like phenotype. PUREdrop bridges computational protein engineering and synthetic cell research, elevating the rational engineering of complex biological function to the next level.
    DOI:  https://doi.org/10.1038/s41467-026-76787-8
  14. bioRxiv. 2026 Jul 30. pii: 2026.05.29.728790. [Epub ahead of print]
    Genetic code expansion enables plant-directed control of bacterial activity.
    Vivian Zhong, Michaela A Jones, Avaniek Cabales, Alice Gevorgyan, René Inckemann, Anna A Johnson, Sumudu S Karunadasa, Amanda M Forti, Shou-Ling Xu, Aditya M Kunjapur, Jennifer A N Brophy.
      Programmable control of microbial gene expression by plant hosts could enable a new generation of precision agricultural biotechnology. Here, using O -methyl-L-tyrosine (OMY) as a model compound, we establish non-canonical amino acids (ncAAs) as a tool for plant-based control of associated microbial activity. We use genetic code expansion to engineer OMY-dependent control of protein synthesis in the soil bacterium Bacillus subtilis. Then, we engineer agronomically diverse plants, including Arabidopsis, tomato and poplar, to biosynthesize OMY. We show that plant-derived OMY can stimulate gene expression in both model and wild soil bacteria while also demonstrating that inducible and tissue-specific expression of a single biosynthetic enzyme by the plant enables on-demand control over microbial activity. This work establishes ncAAs as a tool for programming plant-microbe partnerships.
    DOI:  https://doi.org/10.64898/2026.05.29.728790
  15. Adv Sci (Weinh). 2026 Aug 20. e77159
    Hydraulic Pressure-Programmed Molecular Transport in Tough Hydrogels.
    Yijie Cheng, Shahd Alnasser, Akhiri Zannat, Zhenda He, Jiayi Zeng, Lenan Zhang, Sungmin Hong, Xinyue Liu.
      Molecular transport through polymer networks, including hydrogels and biological matrices, underpins many applications ranging from water filtration and gas separation to drug delivery and cell culture. Conventional strategies for regulating transport in polymer networks primarily focus on tuning molecular diffusion through network mesh size and polymer chemistry, whereas convection is often considered negligible because nanoscale-mesh networks typically exhibit low fluid permeability. Although hydraulic pressure is a well-established driving force for convection in porous media, extending pressure-driven convection to non-porous polymer networks has remained fundamentally challenging because they can undergo substantial deformation or fracture under pressure gradients. Here, we demonstrate that hydraulic pressure applied across mechanically tough and grid-supported hydrogels enables robust and tunable solute transport while maintaining structural integrity. The characteristic transport time can be experimentally modulated by up to 65-fold, consistent with a coupled diffusion-convection model. Beyond tuning transport kinetics, applied pressure enhances size- and charge-dependent transport selectivity by up to 5.4-fold compared to pressure-free conditions. As a proof of concept, we demonstrate pressure-programmed antimicrobial delivery that dynamically controls doxorubicin transport while blocking bacterial penetration. These findings identify pressure-regulated convection as an underexplored mechanism for controlling transport in polymer networks.
    Keywords:  convection; hydraulic pressure; hydrogel membrane; polymer; porous medium
    DOI:  https://doi.org/10.1002/advs.77159
  16. Nature. 2026 Aug;656(8128): 783-784
    Five ways 3D printing is improving lab work.
    Neil Savage.
      
    Keywords:  Chemistry; Engineering; Technology
    DOI:  https://doi.org/10.1038/d41586-026-02535-z
  17. Adv Mater. 2026 Aug 17. e74610
    Stress Transfer Within Microphase-Separated Structures: A Post-Synthetic Strategy to Impart Mechanoresponsiveness to Block Copolymer Materials.
    Kuniaki Ishizuki, Akira Kodaka, Akira Takahashi, Hideyuki Otsuka.
      Mechanoresponsive polymers, which exhibit changes in properties such as color in response to mechanical stimuli, have attracted increasing attention for smart materials. Among various design strategies, mechanophore-incorporated systems are widely used approaches that enable precise molecular-level design and control; however, this approach often suffers from complicated synthesis and limited applicability to existing materials such as block copolymers, which have found widespread industrial use as high-performance materials. Here, we present a post-synthetic strategy enabled by exploiting microphase-separated structures to impart mechanochromism to existing polymer systems while retaining the advantages of mechanophore-based approaches. By exploiting the microphase-separated structure of styrene-butadiene-styrene (SBS) block copolymers, blending with polystyrene bearing a tetraarylsuccinonitrile (TASN) mechanophore enables domain-selective localization of the mechanophore within the rigid domains without chemical modification of the host polymer. The resulting materials exhibit fluorescence upon tensile deformation originating from force-induced TASN cleavage, demonstrating mechanoactivation even under minimal deformation of the hard domains. The mechanoresponse is governed by the molecular weight and content of the mechanophore-containing polystyrene. Importantly, bulk mechanical properties are preserved and can even be enhanced. This strategy establishes a scalable platform for integrating mechanochemical functionality into existing polymer systems.
    Keywords:  block copolymers; mechanochemistry; mechanochromism; mechanophores; phase separation; polymer blends
    DOI:  https://doi.org/10.1002/adma.74610
  18. Sci Adv. 2026 Aug 21. 12(34): eaeg9191
    Evolutionary diversification via modular compliance for self-reconfigurable continuum robots.
    Yilin Cai, Zhefeng Huang, Yifan Wang, Haokai Xu, Yue Chen.
      Modular self-reconfigurable robots promise adaptability through changes in morphology, yet most existing systems remain limited by low functional density, rigid modules, and constrained docking interfaces that restrict scalable locomotion and manipulation. In contrast, biological organisms achieve rich behavioral diversity through repeated compliant segments combined with flexible articulated body architectures to support locomotion, manipulation, and environmental interaction. Here, we present a modular self-reconfigurable continuum robot that exploits modular compliance as a unifying design principle to enable cross-species bioinspired loco-manipulation within a single platform. Each module integrates a continuum backbone for compliant bending and a pair of grippers for omnidirectional, quasi-freeform docking, achieving high functional density within a compact unit. As a result, a small number of modules can assemble into diverse morphologies capable of distinct capabilities. We further develop a morphology-conditioned gait library covering rolling, undulation, crawling, quadrupedal walking, and multisegment manipulation, organized within an evolutionary diversification tree that explicitly links biological locomotion strategies to corresponding robotic assembly patterns. To enable autonomous transitions between configurations, we introduce a unified geometric-topological representation and a self-reconfiguration planner that decomposes reconfiguration into discrete grasping and releasing actions and continuous deformation actions. Hardware experiments demonstrate online self-reconfiguration, followed by integrated loco-manipulation. Together, these results show that embedding compliance at the module level unifies locomotion, manipulation, and self-reconfiguration within a single robotic platform, suggesting a pathway toward more adaptable machines that exhibit organism-like behaviors across species.
    DOI:  https://doi.org/10.1126/sciadv.aeg9191
  19. Cell Syst. 2026 Aug 11. pii: S2405-4712(26)00184-5. [Epub ahead of print] 101702
    A diversified consortium of engineered biosensors enables multi-target quantification.
    Alyssa Jasmine Chiang, Nicholas Csicsery, Richard O'Laughlin, Leo Baumgart, Elizabeth Stasiowski, Phuc Nguyen, Austin Doughty, Myra Ashraf, Raegan Mink, Elina C Olson, Michael Ferry, Adam M Feist, Nan Hao, Karsten Zengler, Jeff Hasty.
      Whole-cell biosensors (WCBs) offer rapid, cost-effective monitoring of environmental contamination. Efforts to optimize detection of isolated target analytes under laboratory conditions have achieved vastly improved performance and set the stage for WCB deployment in complex environments. We propose a framework that leverages cross-reactivity of single-target WCBs to quantify multiple targets using supervised machine learning. Specifically, we engineer six sensors for heavy metal contaminants in laboratory E. coli. We then evolve the strain to generate five chassis with improved growth in seawater conditions and transform them with the sensors to create a set of 30 variants. The variant responses are characterized with microfluidics, revealing significant diversity. Leveraging this diversity, we combinatorially quantify multiple analytes with a machine learning model that takes an in silico consortium of response inputs and outperforms single-target WCBs in over 90% of test samples. These results form a generalizable framework that facilitates WCB translation toward settings beyond the laboratory. A record of this paper's transparent peer review process is included in the supplemental information.
    Keywords:  combinatorial biosensing; consortium; differential sensing; evolution; machine learning; microfluidics; synthetic biology; whole-cell bacterial biosensors
    DOI:  https://doi.org/10.1016/j.cels.2026.101702
  20. ACS Appl Mater Interfaces. 2026 Aug 20.
    Toward Long-Term Bioelectronic Interfaces: Mechanical Compliance Meets Immunocompatibility.
    Zihao Zhu, Xianchi Zhou, Yijing Yin, Jian Ji, Youxiang Wang, Peng Zhang.
      Achieving chronic stability in implantable bioelectronics requires more than strong initial performance. It depends on the synergistic integration of mechanical compliance, electrochemical functionality, and immunocompatibility, because failure in any dimension can lead to micromotion-induced damage, signal instability, or chronic inflammation. Here, we present a framework for engineering bioelectronic interfaces under immune surveillance by analyzing multiscale triggers of the foreign body response, including geometric intrusion, modulus mismatch, and interfacial chemistry. We evaluate representative flexible and stretchable metal-based systems that improve mechanical matching but often lack bioactive or immunomodulatory design. We then discuss conductive hydrogels as hydrated conductors that can bridge mechanical and electrochemical mismatches, while emphasizing that their host response cannot be assumed and must be engineered. Finally, we outline material-level strategies-dopant selection, network architecture, and molecular functionalization-and discuss remaining challenges in micro/nanofabrication, hybrid integration, and application-oriented molecular design.
    Keywords:  bioelectronic interfaces; conductive hydrogels; foreign body response; immunocompatibility; mechanical compliance
    DOI:  https://doi.org/10.1021/acsami.6c13701
  21. Curr Protoc. 2026 Aug;6(8): e70443
    A Protein Editing Method to Modify Proteins in Live Mammalian Cells.
    Jenna N Beyer, Kaitlyn Toy, George M Burslem.
      Protein editing, as mediated by protein trans-splicing, offers the ability to manipulate, label, and modify proteins in vitro and in live mammalian cells. This ability to observe and control proteins with this high resolution is a burgeoning area of interest within the chemical biology field. In this protocol, we outline the general approach for setting up a cellular protein editing experiment, emphasizing the planning process for a successful protein editing experiment. Additionally, we include methods to install and subsequently label a click chemistry handle p-azido-phenylalanine, a non-canonical amino acid (ncAA) within the intein donor, such that this ncAA and any label can be edited into a protein in live mammalian cells. Overall, we anticipate that this protocol should serve as a generalizable roadmap for planning and carrying out a protein editing experiment. © 2026 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Expression of intein donor containing pAzF Basic Protocol 2: Purification and labeling of recombinant intein donor Basic Protocol 3: Preparation of mammalian cells for editing experiments Basic Protocol 4: Protein editing via electroporation.
    Keywords:  biology; chemical biology; click chemistry; genome editing; noncanonical amino acid; protein Editing
    DOI:  https://doi.org/10.1002/cpz1.70443
  22. Proc Natl Acad Sci U S A. 2026 Aug 25. 123(34): e2536343123
    Morphogenesis of bacterial colonies in liquid crystalline environments.
    Sebastian Gonzalez La Corte, Thomas G J Chandler, Saverio E Spagnolie, Ned S Wingreen, Sujit S Datta.
      Natural bacterial habitats are often complex fluids with viscoelastic and anisotropic responses to stress; for example, they can take the form of liquid crystals (LCs), with elongated microscopic constituents that collectively align while still retaining the ability to flow. However, laboratory studies typically focus on cells in simple liquids or complex fluids with randomly oriented constituents. Here, we show how interactions with LCs shape bacterial proliferation in multicellular colonies. Using experiments, we find that in a nematic LC, cells of the multiple species we tested all form aligned single-cell-wide "chains" as they reproduce. As these chains lengthen, they eventually buckle in a highly localized manner. By combining our measurements with a continuum mechanical theory, we demonstrate that this distinctive morphogenetic program emerges because cells are kept in alignment due to the LC's elasticity; as each chain lengthens, growth-induced viscous stresses along its contour eventually overcome the elasticity of the surrounding nematic, leading to buckling. Our work thus reveals and provides mechanistic insight into the previously overlooked role of LCs in sculpting bacterial life in complex environments.
    Keywords:  active matter; bacteria; colony growth; liquid crystal; nematic
    DOI:  https://doi.org/10.1073/pnas.2536343123
  23. ACS Chem Biol. 2026 Aug 19.
    Facile Siderophore Assembly Enables Bacterial Delivery of Nucleic Acid Therapeutics.
    Harshitha Ramu, Peter Kuijken, Georgia Poulladofonou, Mathijs J Pals, Daniel Summerton, Yong-Fu Li, Willem Arend Velema.
      Antibiotic resistance is an increasing threat to modern medicine that calls for the discovery of new antibiotics. RNA targeting is a promising approach for antibiotic development. In particular, antisense antibiotics, dubbed ASObiotics, are an exciting class of oligomers that show promise as powerful antibiotic agents. However, limited bacterial uptake has hampered their widespread use. Exploiting bacteria's own machinery in transporting cargo into the cell through siderophore-mediated delivery can address this obstacle. Here, we report the design of a tris-catechol-type siderophore that allows for the assembly on the backbone of antisense therapeutics during their solid-phase peptide synthesis. This approach fully negates the need for challenging siderophore synthesis and conjugation to the antisense therapeutic. The resulting ASObiotics display potent submicromolar activity against Escherichia coli. Through a series of competition and knockout experiments, we elucidated that ASObiotic delivery is accomplished through the Fiu receptor. On-target engagement was established through RT-qPCR, lacZ reporter assays, and Western blot. We further demonstrate the potential use of these siderophore-antisense conjugates as antibiotics against Bacillus subtilis and Acinetobacter baumannii.
    DOI:  https://doi.org/10.1021/acschembio.6c00323
  24. bioRxiv. 2026 Aug 06. pii: 2026.08.05.743105. [Epub ahead of print]
    PANCS-Inhibitors: A rapid method to directly select for protein-protein interaction inhibitors.
    Matthew J Styles, Victoria Cochran Xie, Sandrine Legault, Joshua A Pixley, Bryan C Dickinson.
      Aberrant protein-protein interactions (PPIs) drive myriad diseases. Inhibiting these PPIs often relies on discovering molecules that bind to one of the proteins and hoping that this binding inhibits the PPI. Molecular binder discovery often takes months, but a discovery process that ensures that the resulting molecule not only binds a target protein, but selectively inhibits a target PPI, could dramatically accelerate these endeavors. Here, we develop Phage-Assisted Non-Continuous Selection of PPI Inhibitors (PANCS-Inhibitors): a rapid screening platform that directly selects for molecules capable of disrupting a pre-formed PPI. We demonstrate this new platform using three clinically relevant oncogenic PPIs: KRas-Raf, Mdm2-p53, and Myc-Max. PANCS-Inhibitors can be used to both improve known PPI inhibitors and for de novo discovery of mini-protein PPI inhibitors that function in mammalian cells. This platform has the potential to rapidly generate inhibitors for many clinically relevant PPIs, which can be used as starting points for therapeutic development.
    DOI:  https://doi.org/10.64898/2026.08.05.743105
  25. ACS Appl Mater Interfaces. 2026 Aug 20.
    Surface-Engineered Poly(ethylene oxide)-Grafted Quantum Dot Inks for Green-Solvent-Processed Electroluminescent Devices.
    Moon-Chul Ryu, Gyu Jin Shin, Ho Seok Heo, Seung Ah Lee, Tae-Young Heo, Kangtaek Lee, Jun Hyup Lee, Soo-Hyung Choi.
      Quantum dots (QDs) are promising emissive materials for next-generation optoelectronics, but conventional oleic acid (OA) capping necessitates toxic, nonpolar solvents such as toluene and chloroform, hindering environmentally sustainable solvent-based processing. Here, we report a green, solution-processable ligand-exchange strategy in which thiol-terminated poly(ethylene oxide) (PEO-SH) replaces OA on QDs, enabling stable dispersion in ethanol and water. By tuning the molecular weight of PEO, we identify PEO with Mn ≈ 2000 g/mol as an optimal ligand that provides a balanced combination of chain length and surface coverage, resulting in long-term colloidal stability and high photoluminescence quantum yield in polar media. Using these QD-PEO2k inks, we fabricate multilayer quantum dot light-emitting diodes (QLEDs) from ethanol and water/ethanol co-solvents, achieving a maximum external quantum efficiency of 2.12% and a current efficiency of 9.19 cd A-1. These results successfully serve as a proof-of-concept for generating functional electroluminescence from water/alcohol-based QD inks. Ultimately, this work establishes a foundational step toward reducing toxic solvent dependency and advancing sustainable manufacturing in solution-processed optoelectronics.
    Keywords:  electroluminescence; green processing; ligand exchange; polymer brushes; quantum dots
    DOI:  https://doi.org/10.1021/acsami.6c10538
  26. ACS Macro Lett. 2026 Aug 18. 15(8): 1069-1079
    Beyond Stimuli Responsiveness: Toward Decision-Making Polymers.
    Navid Rabiee, Sidi A Bencherif.
      Stimuli-responsive polymers have transformed macromolecular science by enabling materials that dynamically alter their structure and function in response to environmental cues. Despite these advances, however, most responsive polymers remain fundamentally reactive rather than interpretive, operating through direct stimulus-response coupling without contextual evaluation. In this viewpoint, we propose that polymer science is approaching a conceptual transition from stimuli-responsive matter to decision-making matter, where materials are engineered not only to respond but also to integrate, discriminate, and selectively act upon complex, multivariate inputs. We define decision-making polymers as systems whose outputs emerge from multistimulus coupling, nonlinear response topology, internal state memory, and path-dependent dynamics. We further propose that such behavior can be understood through programmable free-energy landscapes that enable context-dependent occupation of competing metastable states. We discuss physicochemical strategies for encoding decision behavior, including coupled responsive motifs, sequence-defined architectures, spatial heterogeneity, and memory-bearing polymer networks, and outline a framework for evaluating polymer performance based on signal selectivity, conditional susceptibility, and adaptive state evolution. Together, this work positions decision-making polymers as a promising new direction in macromolecular science for autonomous operation in complex biological and technological environments. Here, decision-making refers to physicochemically encoded, context-selective state selection rather than cognition.
    DOI:  https://doi.org/10.1021/acsmacrolett.6c00272
  27. Nat Biotechnol. 2026 Aug 17.
    Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells.
    Hyuncheol Jung, Pascal Devant, Carter Ching, Mineto Ota, Emma Dann, Ronghui Zhu, Chandrima Modak, Ana Vasquez-Ibarra, Jennifer R Hamilton, Zachary Steinhart, Wayne Ngo, Luis Sandoval, Jae Hyung Jung, Jae Hyun J Lee, Da Xu, Meirui An, Esha Urs, Peixin Amy Chen, Vincent Allain, Takuya Tada, Luke A Gilbert, Brian R Shy, Jonathan K Pritchard, James K Nuñez, Nathaniel R Landau, David R Liu, Justin Eyquem, Jennifer A Doudna, Alexander Marson, Julia Carnevale.
      Primary human myeloid cells hold promise for immunotherapies, yet efficient, scalable technologies for engineering and screening in these cells remain limited. Here we present a virus-like particle (VLP)-based toolkit that delivers diverse CRISPR editing modalities to human monocytes, macrophages and dendritic cells with high efficiency while preserving viability and innate immune responsiveness. VLP-mediated delivery of ribonucleoproteins supports gene knockout, base editing and epigenetic silencing. Combined with adeno-associated virus-mediated donor delivery, this approach enables site-specific integration of large DNA sequences by homology-directed repair. We developed SLICeVLP, which pairs sgRNA delivery by VPX-lentivirus with Cas9 protein delivery by engineered VLPs, and used it for pooled loss-of-function and Perturb-seq screens in human macrophages. We uncovered regulators of tumor necrosis factor (TNF) and CD80 expression, converging on TNFAIP3 as a central regulator of inflammatory polarization. TNFAIP3 ablation drove a proinflammatory state resistant to suppressive repolarization and enhanced cytotoxicity in chimeric antigen receptor macrophages. This system enables unbiased functional genomics in primary human myeloid cells, with implications for myeloid cell therapy design.
    DOI:  https://doi.org/10.1038/s41587-026-03258-2
  28. Bioconjug Chem. 2026 Aug 19. 37(8): 1523-1529
    Next-Generation Glycan Materials Bridging Organic and Inorganic Chemistry.
    Matthew M Campbell, Jorge A Carmona, Charlotte E Hantus, Anna K Keum, Rohan Pillai, Sarah K Vest, Julia M Stauber.
      The central roles that glycans play in cell communication, adhesion, signal transduction, and pathogen recognition have driven growing interest in understanding glycan-mediated protein recognition events. Because protein-glycan binding is governed by three-dimensional carbohydrate presentation, precise structural control over synthetic glycan assemblies is essential for understanding fundamental principles underlying the recognition of both natural and artificial glycans. Most conventional glycomimetics, however, often lack the precise structural organization characteristic of native glycans, which limits detailed understanding of the architectural parameters that dictate their function. Molecular inorganic glycan assemblies provide an emerging platform that provides control over glycan valency, spacing, and topology to achieve programmable recognition behavior. This Viewpoint highlights the development of metal-templated glycan complexes that afford well-defined architectures with tunable recognition behavior and biological function and also discusses developing opportunities at the interface of inorganic and organic chemistry, glycobiology, and biomolecular design.
    DOI:  https://doi.org/10.1021/acs.bioconjchem.6c00321
  29. ACS Nano. 2026 Aug 18. 20(32): 22909-22918
    Tunable DNA-Stabilized Bicelles as Nanoscale Membrane Mimetic Systems.
    Juliette Gevers, Koen Martens, Maarten Fauvart, Steven Vanuytsel, Gerard Carrera I Cardona, Florian Lucas, Gangamallaiah Velpula, Steven De Feyter, Peter Dedecker, Giovanni Maglia, Pol Van Dorpe.
      Membrane proteins are central to cellular function and constitute the majority of drug targets, yet their structural and functional characterization at the single-molecule level requires stabilization within a native-like lipid environment. Here, we introduce a robust and tunable DNA origami nanodisc that incorporates inherently planar lipid bicelles as a promising platform for future membrane protein studies. The highly charged and bulky DNA envelope acts as a structural stabilizer, enabling efficient bicelle incorporation and stabilization. Moreover, bilayer geometry can be precisely tuned by adjusting the long-chain to short-chain lipid ratio (q-ratio), yielding diameters from ∼18 to 26 nm. As a proof of concept, we demonstrate the successful association of Fragaceatoxin C (FraC) monomers, a pore-forming membrane protein, with the DNA-stabilized bicelles. Potential applications of this versatile platform include high-throughput membrane protein analysis, hydrophobic drug delivery, and hybrid nanopore sensing.
    Keywords:  DNA nanotechnology; DNA origami nanodisc; DNA-stabilized bicelle; lipid bicelle; membrane mimetics; membrane proteins
    DOI:  https://doi.org/10.1021/acsnano.6c09188
  30. ACS Appl Bio Mater. 2026 Aug 17. 9(16): 7441-7452
    Tuning of Bacterial Cellulose Hydrogel Architecture during Fermentation through Polymer-Modified Growth Media.
    Firoozeh Babayekhorasani, Maryam Hosseini, Goldina Kwandou, Jie Song, Patrick T Spicer.
      The formation of bacterial cellulose pellicles by Acetobacter xylinum is investigated in growth media supplemented with sodium alginate (SA) or carboxymethylcellulose (CMC). Both polymers influence bacterial cellulose assembly during growth, but through distinct physicochemical mechanisms. In SA-containing media, increased viscosity reduces bacterial mobility and promotes the formation of denser pellicles with reduced interlayer spacing and porosity, without substantially affecting cellulose production. In contrast, under the acidic culture conditions used in this study, CMC undergoes pH-dependent conformational changes and adsorption-mediated interactions with cellulose fibrils, promoting local aggregation and bundle formation while reducing pellicle thickness and dry mass. By tuning medium viscosity and fiber-polymer interactions during bacterial growth, it is possible to direct the assembly of cellulose nanofibrils, enabling the design of hydrogels with tailored density, porosity, and microstructural properties for applications such as biomedical scaffolds and tissue engineering matrices.
    Keywords:  bacterial cellulose hydrogels; biofilm microstructure; polymer-induced fibril bundling; rheology-mediated densification
    DOI:  https://doi.org/10.1021/acsabm.6c00516
  31. Phys Rev E. 2026 Jul;114(1-2): 015420
    Partitioning law of polymer chains into flexible polymer networks.
    Haruki Takarai, Takashi Yasuda, Naoyuki Sakumichi, Takamasa Sakai.
      The equilibrium partitioning of linear polymer chains into flexible polymer networks is governed by intricate entropic constraints arising from the configurational degrees of freedom of both chains and networks; however, a quantitative understanding remains elusive. Using model hydrogels with precisely defined network structures, we experimentally demonstrate a universal law governing the partitioning of linear polymers into flexible polymer networks. We establish a label-free contactless method to measure the partition ratio, based on the increase in the osmotic pressure induced by the partitioning of the external polymer chains. Moreover, we reveal a universal law in which the partition ratio is determined solely by R_{g}/l_{cycle}, where R_{g} is the gyration radius of the polymer chain and l_{cycle}≡ξ^{-1/3} is the characteristic mesh size of the network, defined by the cycle rank ξ, i.e., the number density of elastically effective cycles.
    DOI:  https://doi.org/10.1103/vvg5-dhy2
  32. bioRxiv. 2026 Jul 30. pii: 2026.07.29.741625. [Epub ahead of print]
    In vivo reconstruction of the cell lineage history of a developing mouse with DNA Typewriter, from zygote to late organogenesis.
    Qi Yu, Haedong Kim, Sophie Seidel, James F Acosta-Clark, Beth K Martin, Kyle O'Connor, Riza M Daza, Molly Gasperini, Jenny F Nathans, Maggie Lam, Elena Gamo, Shruthi VijayKumar, Lauren Kuo, Jean-Benoît Lalanne, Kamen Simeonov, Marion Pepper, Cole Trapnell, Jesse M Gray, Junhong Choi, Chengxiang Qiu, Jay Shendure.
      The complete cell lineage of C. elegans , mapped over four decades ago, was tractable because the animal is small, transparent, and lineage invariant 1 . Most animals are none of these, having orders of magnitude more cells, being opaque, and developing with substantial stochasticity 2 . Since 2016, genome editing-based lineage tracing has opened the door to dense cell lineage reconstruction in such organisms 3-8 , but delivering on that promise has proven technically challenging. Here we apply DNA Typewriter 9-11 , a prime editing-based recorder that writes stochastic symbolic insertions to an engineered genomic TAPE in strictly sequential order, to trace mouse development from zygote (E0) to late organogenesis (E13.5). We introduce constructs encoding a prime editor, engineered prime editing guide RNAs (epegRNAs), and Pol-III-driven circularized TAPE RNA (circTAPE) into wildtype zygotes by pronuclear injection (PNI), then assay embryos by single-nucleus transcriptional profiling (sci-RNA-seq3) 12 with paired circTAPE recovery. From one E13.5 embryo bearing ∼7 integrations of a constitutively expressed prime editor and 11 integrations of 6-unit circTAPE, we recover ∼1.75M single-nucleus transcriptomes and reconstruct a time-calibrated phylogeny of 1,340,794 annotated cells with parsimony-based node support. The first cell division is marked unequivocally, and although the resulting blastomeres contribute asymmetrically to the embryo proper, they are fate-neutral and serve as internal replicates that reproduce every finding. A modest cohort of pre-gastrulation founders dominates the embryo, with inequality exceeding neutral expectation within one to two cell cycles of founder allocation, yet these founders remain broadly multipotent; a second phase of clonal dominance arises in specific lineages during organogenesis. At the finest scale, sibling cells share cell type 9-fold in excess of chance, reaching 68- to 107-fold for cell types arising from spatially restricted founder pools, while the recent differentiations of organogenesis are legible in the heterotypic structure of terminal clades. From clade co-occurrence alone, we recover germ-layer organization and a dated hierarchy of cell-type couplings with branch points from E8.5 onwards. Finally, by integrating these data with our single-cell time-series of mouse development 13 , we impute transcriptional states and annotations for the majority of internal nodes and recover established state histories for diverse cell types. All data are made freely available, together with NextCell , an interactive browser for this annotated cellular phylogeny of mouse development from zygote to late organogenesis.
    DOI:  https://doi.org/10.64898/2026.07.29.741625
  33. Nat Biotechnol. 2026 Aug 19.
    Massive-scale parallel gene synthesis with oligonucleotide hybridization.
      
    DOI:  https://doi.org/10.1038/s41587-026-03290-2
  34. bioRxiv. 2026 Aug 04. pii: 2026.08.02.742326. [Epub ahead of print]
    A Compact, Standalone & Battery-Powered 3D Organoid-on-Chip System with Programmable Flow Control.
    Raviraj Thakur, Vaibhav Murthy, Samuel Olson, Emma Wolcott, Darya Budkina, Francis Anderson, Ting Zheng, Austin Wright, Jeremy Copperman, Luiz Bertassoni, Ellen Langer, Alexander E Davies.
      Organoids-on-chip combine the 3D complex microenvironment and cellular composition of organoids with microfluidic flow, increasing nutrient-waste exchange and mimicking the contributions of in vivo interstitial and vascular flow. However, the widespread adoption of organoid-on-chip platforms is limited by the lack of incubator-friendly flow control systems. Existing approaches often rely on commercially available syringe or peristaltic pumps, but these are bulky, lack scalability, and present a significant barrier for clinical translation. To circumvent these issues, we present the Compact Active Perfusion Standalone Organoid-on-Chip (CAPS-OC) platform, a fully integrated and battery-powered microfluidic system capable of culturing organoids in active media flow. To achieve this, we introduce a novel low-power mechanism of pressure pulse generation using an off-the-shelf compact rotary actuator (CRA), and package it into a compact electromechanical assembly. This assembly provides timed pneumatic inputs to achieve programmable control of membrane-based peristaltic pumps, with ∼100 µL/hr dynamic range achieved on a custom microfluidic organoid chip. We biologically validated this system by culturing pancreatic cancer organoids derived from a Kras LSL-G12D/+ ; Trp53 LSL-R172H/WT ; Pdx1-Cre (KPC) genetically engineered mouse model. We found that our chip enhances proliferation and helps sustain a population of larger (>150 µm) organoids compared to standard dome based static culture. Additionally, through immunostaining, we observe that KPC organoids cultured in the chip show more aggressive PDAC phenotype with reduced nuclear expression of GATA6, whereas organoids in static culture retain less aggressive classical- like subtype. Finally, testing of a RAS inhibitor drug, daraxonrasib, on the KPC organoids on chip showed size-based sensitivity elucidating the impact of active perfusion on the drug diffusion kinetics. Altogether, we establish CAPS-OC as a valuable tool for the bioengineering community and for clinically translating organoid model systems.
    DOI:  https://doi.org/10.64898/2026.08.02.742326
  35. Nature. 2026 Aug 19.
    The HydroGym reinforcement learning platform for fluid dynamics.
    Christian Lagemann, Sajeda Mokbel, Miro Gondrum, Mario Rüttgers, Yuning Wang, Pol Suárez, Ludger Paehler, Deniz A Bezgin, Aaron B Buhendwa, Jared L Callaham, Samuel Ahnert, Nicholas Zolman, Xiao Shao, Jean-Christophe Loiseau, Nikolaus A Adams, Matthias Meinke, Wolfgang Schröder, Kai Lagemann, Esther Lagemann, Ricardo Vinuesa, Steven L Brunton.
      Effective control of fluid flows is critical across transportation, energy and medicine, where it can increase lift, reduce drag, enhance mixing and attenuate noise1-3. Yet fluids are notoriously difficult to control because they involve high-dimensional, nonlinear and multiscale dynamics that resist conventional approaches4-6. Reinforcement learning has driven remarkable progress in fields such as protein folding and complex games, which have shared benchmarks and standardized environments7-10. Fluid dynamics has lacked such infrastructure, so each controller is typically tuned to a single geometry and operating condition, making progress difficult to accumulate, transfer and compare11-13. Here we introduce HydroGym, a solver-independent reinforcement learning platform providing more than 60 validated, openly available flow control environments spanning from canonical laminar flows to complex turbulent flows, with systematic progression in the Reynolds number up to Re = 4 × 105, and Mach number variations in two and three dimensions. Across these environments, agents repeatedly discover robust control principles, including boundary layer manipulation, disruption of acoustic feedback and reorganization of turbulent wakes. Critically, we demonstrate a proof of concept for zero-shot transfer, in which agents that are trained exclusively in inexpensive surrogate environments are deployed to challenging real-world scenarios such as a three-dimensional wing section. We achieve a 38% reduction in local skin friction while reducing exploration costs by four orders of magnitude compared with direct on-wing optimization. As this transfer exploits shared near-wall physics, the breadth of generalization remains open, suggesting a new pathway for research toward policy generalization across computationally prohibitive simulation environments. By offering a common, extensible foundation for reproducible research, HydroGym moves flow control from isolated case studies toward a cohesive community effort.
    DOI:  https://doi.org/10.1038/s41586-026-10917-6
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