bims-enlima Biomed News
on Engineered living materials
Issue of 2026–09–13
25 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool
  1. Volumetric 3D printing of microalgae-based engineered living materials.
  2. Controlling viscoelastic behavior and microstructural organization in engineered living materials using synthetic adhesins and rheometry.
  3. Autonomous Control of Gene Expression Using Endogenous Transcription Signals.
  4. Synthetic biology.
  5. On-demand glycemic control by engineered bacteria.
  6. Engineered living materials: integration of living and nonliving systems.
  7. Phage-assisted continuous evolution of enzymes for noncanonical tyrosine biosynthesis.
  8. A monolithic fabrication platform for intrinsically stretchable polymer transistors and complementary circuits.
  9. Biocompatible Microscale DNA Hydrogels with Programmable Swelling and Sequence-Specific Dissolution.
  10. Let there be multifunctionality: Uncovering the dynamical zoo of the AC-DC genetic circuit.
  11. Probing the proteome at cellular scale.
  12. Biomaterials in organoid research: current state and future directions.
  13. Tailored living mycelium macerate for reproducible flexible actuators.
  14. A boost for CAR T cell therapy.
  15. Refractive-index-matched jammed microgel assemblies enable volumetric printing of porous hydrogel architectures.
  16. Molecular modifier aids melting of MOFs.
  17. A Non-Living, Microbe-Based Surface Coating Promotes Tubeworm and Coral Settlement.
  18. Activation-independent capture of free fatty acids at the bacterial cell envelope by BrtB.
  19. Engineering biosensors to enhance monoterpene indole alkaloid production in yeast.
  20. Curved Odd Elasticity.
  21. Drug delivery gets subcellular.
  22. Extracellular matrix composition and stiffness regulates progesterone responsiveness and decidualization.
  23. Robust cellular transformations of PET deconstruction products by import of glycol esters.
  24. Dense RNA motif modifications enable robust in vivo prime editing and enhance efficiencies of diverse editing systems.
  25. Layer-by-layer nanoparticle outer polyelectrolyte impacts protein corona formation.
  1. Trends Biotechnol. 2026 Sep 08. pii: S0167-7799(26)00369-0. [Epub ahead of print]
    Volumetric 3D printing of microalgae-based engineered living materials.
    Christoph A Spiegel, Eva Blasco.
      In their work, Windisch et al. demonstrate the successful adaptation of volumetric 3D printing to photosynthetically active green microalgae-based engineered living materials (ELMs), addressing key fabrication challenges associated with light scattering and absorption in cell-laden materials. Their work expands the fabrication toolbox for geometrically complex ELMs and highlights volumetric printing as a promising approach for developing functional photosynthetic living materials.
    DOI:  https://doi.org/10.1016/j.tibtech.2026.08.016
  2. Acta Biomater. 2026 Sep 08. pii: S1742-7061(26)00576-3. [Epub ahead of print]
    Controlling viscoelastic behavior and microstructural organization in engineered living materials using synthetic adhesins and rheometry.
    Stefana A Costan, Kira M Hallerbach, Samuel Y Kim, Chris Camp, Minkyu Kim, Ingmar H Riedel-Kruse.
      Engineered living materials (ELMs) at the multicelluar level represent an innovation that promises programmable properties for various applications. However, the rational tuning of the mechanical properties of such ELMs from first principles remains a challenge. Here we use synthetic cell-cell adhesins to systematically characterize how rheological and viscoelastic properties of multicellular materials made from living bacteria can be tuned through adhesion strength, cell size, cell shape, and adhesion logic. We find that many of the previous results obtained for non-living materials also apply to bacterial ELMs. Additionally, the incorporation of synthetic adhesins, combined with the adaptability of bacterial cells in modifying various cellular parameters, constitutes a new approach for the precise control over material properties. Furthermore, we demonstrate that rheology is a powerful tool for actively shaping the microscopic structure of ELMs, enabling control over cell aggregation and particle rearrangement, a key feature for complex material design. These results deepen our understanding of tuning the viscoelastic properties and fine structure of ELMs for bioprinting, microbial consortia design, and biomedical applications. Statement of significance The fields of Engineered Living Materials (ELMs) and Synthetic biology undergo rapid synergistic advancements, with bacterial and eukaryotic cells serving as modular building blocks for programmable materials. A critical challenge lies in the precise control and tunability over the mechanical and structural properties of ELMs. This paper demonstrates (1) the tunability of material viscoelasticity through key cellular parameters, i.e., adhesin strength, adhesion logic, cell shape, and multi-component mixing ratios; and (2) the generation of spatially defined colloidal consortia, mesoscopic structuring, pore formation and defect minimization through rheological manipulations. This paper bridges gaps between synthetic biology and materials science by providing a quantitative basis for ELM design and characterization, and by extending results from non-living particle suspensions to ELMs.
    Keywords:  Bacteria; Engineered living materials; Rheology; Structure formation; Synthetic adhesins; Synthetic biology; Viscoelasticity
    DOI:  https://doi.org/10.1016/j.actbio.2026.08.044
  3. Biotechnol Bioeng. 2026 Sep 09.
    Autonomous Control of Gene Expression Using Endogenous Transcription Signals.
    Pakpoom Subsoontorn, Drew Endy, Olivier Borkowski.
      Autonomous cell-based control of heterologous gene expression can simplify batch-culture bioprocessing by eliminating external monitoring and extrinsic control of culture conditions. Existing approaches use auto-induction media, synthetic cell-cell communication systems, or application-specific biosensors. A simpler, resource-efficient, and general-purpose expression control system responsive to common changes during batch culture would be highly valuable. We used native E. coli promoters, including PhdeA, PdpS, PfumA, PrpoA, PrpoS, PgadA, and PyiaG, and recombinase-based switches to repurpose endogenous transcription signals for control of heterologous gene expression. Specifically, natural changes, covering 1-2 orders of magnitude across growth phases, in transcription from endogenous promoters result in recombinase expression at the exponential-to-stationary phase transition. So-expressed recombinases invert a constitutive promoter regulating expression of arbitrary heterologous genes amplifying the endogenous transcriptional input signal by more than 10-fold. We realized reversible and single-use switching with reduced static and dynamic cell-to-cell variation and overall expression amplification. We used "off-the-shelf" genetic parts and abstraction-based composition frameworks to realize reliable forward engineering of our synthetic genetic systems. We engineered autonomous control systems for regulating heterologous gene expression. Our system uses generic endogenous promoters to sense and control heterologous expression during growth-phase transitions. Our system does not require specialized auto-induction media, production or activation of quorum sensing, or the development of application-specific biosensors. Cells programmed to control themselves could simplify existing bioprocess operations and enable the development of more powerful synthetic genetic systems. Modern biotechnology uses engineered microbes to manufacture molecules that are incorporated into medicines, flavors, fuels, and other materials. Making molecules inside cells requires enzymes, whose expression levels and timing need to be optimized to maximize final product yields. Many engineered microbes use enzymes that should only be expressed during the later stages of cell growth to avoid overconsumption of resources or accumulation of toxic intermediates. Here, we develop simple genetic devices that enable engineered cells to control themselves, automatically switching on or off enzyme expression during batch cell culture. Unlike existing approaches, our devices do not require specialized growth media or wasteful synthesis of cell-cell signaling molecule.
    Keywords:  autonomous control; growth phase; protein production; synthetic biology; transcription signal
    DOI:  https://doi.org/10.1002/bit.70377
  4. Nat Biotechnol. 2026 Sep;44(9): 1447
    Synthetic biology.
      
    DOI:  https://doi.org/10.1038/s41587-026-03289-9
  5. Nat Biotechnol. 2026 Sep;44(9): 1448
    On-demand glycemic control by engineered bacteria.
    Dario Ummarino.
      
    DOI:  https://doi.org/10.1038/s41587-026-03323-w
  6. Bioresour Technol. 2026 Sep 09. pii: S0960-8524(26)01870-5. [Epub ahead of print] 135788
    Engineered living materials: integration of living and nonliving systems.
    Haoran Yin, Wei Wei, Danshan Zhao, Runxin Zhang, Liyuan Zhu, Chao Ye, Tianqiong Shi, Yuetong Wang.
      Engineered living materials (ELMs) are an emerging class of biohybrid materials that integrate living cells with nonliving matrices to create systems capable of sensing, responding, adapting, and, in some cases, self-repairing. By coupling the programmability of synthetic biology with the structural tunability of polymeric, inorganic, or composite scaffolds, ELMs offer a new route toward materials that perform dynamic functions beyond those of conventional biomaterials. However, ELMs remain limited by key challenges, including the trade-off between mechanical robustness and cellular viability, restricted mass transport, unstable long-term function, bio-abiotic interfacial complexity, biosafety risks, and scalable manufacturing. This review outlines recent advances in ELM design, fabrication, and applications, emphasizing chassis engineering, smart matrices, bioprinting, in situ growth, and translational potential in medicine, environmental remediation, and biomanufacturing. It further discusses emerging strategies, including multicellular consortia, genetic biocontainment, and artificial intelligence (AI)-guided inverse design, for developing predictable, safe, and adaptive living materials.
    Keywords:  Bio-abiotic interface; Engineered living materials; Smart matrix; Synthetic biology
    DOI:  https://doi.org/10.1016/j.biortech.2026.135788
  7. Proc Natl Acad Sci U S A. 2026 Sep 15. 123(37): e2614167123
    Phage-assisted continuous evolution of enzymes for noncanonical tyrosine biosynthesis.
    James S Andon, Abhijit Behera, Debashrito Deb, Amy M Weeks, Andrew R Buller, Tina Wang.
      Genetic code expansion introduces new-to-nature chemical moieties into ribosomally synthesized proteins. In practice, the scope of functional groups that can be accessed using this method is often limited by noncanonical amino acid (ncAA) availability. Producing ncAAs directly in cells can circumvent poor ncAA uptake or commercial unavailability, but limited enzymes suitable for this application exist. In vitro evolution campaigns have yielded synthetically useful "ncAA synthases," but these enzymes are optimized for preparative-scale synthesis and their activities often do not translate well to cellular biosynthesis. Thus, expanding strategies to engineer enzymes specifically for ncAA production within cells will benefit further implementation of genetic code expansion. Here, we use phage-assisted noncontinuous and continuous evolution to evolve enzymes for improved synthesis of noncanonical tyrosine derivatives in Escherichia coli. Using simple serial passaging, we uncovered mutations that doubled the production of an expensive ncAA, 3-methoxytyrosine, by tyrosine phenol lyase, and furthermore evolved variants that enable 3-iodotyrosine biosynthesis, a transformation the parent enzyme is unable to perform in cells. Additionally, we evolved a recently reported tyrosine synthase for improved production of 3-halogenated tyrosines, identifying variants that exhibit high activity even at low substrate concentrations owing to a ~eightfold reduction in KM. Our results demonstrate that phage assisted evolution can be used to rapidly improve the activity of enzymes for ncAA production in cells.
    Keywords:  biosynthesis; directed evolution; genetic code expansion; noncanonical amino acids; phage-assisted continuous evolution
    DOI:  https://doi.org/10.1073/pnas.2614167123
  8. Device. 2026 Aug 21. pii: 101204. [Epub ahead of print]4(8):
    A monolithic fabrication platform for intrinsically stretchable polymer transistors and complementary circuits.
    Yujia Yuan, Chuanzhen Zhao, Margherita Ronchini, Yuya Nishio, Donglai Zhong, Can Wu, Hyukmin Kweon, Zehao Sun, Rachael K Mow, Yuran Shi, Lukas Michalek, Haotian Wu, Qianhe Liu, Weichen Wang, Yating Yao, Zelong Yin, Junyi Zhao, Zihan He, Ke Chen, Ruiheng Wu, Jiuyun Shi, Jian Pei, Zhenan Bao.
      Stretchable organic field-effect transistors (OFETs) provide signal conditioning for bioelectronics while offering tunable mechanical and chemical properties, but their fabrication remains materialspecific and difficult to extend to complementary circuits, where sequentially patterning of multiplex semiconductors often degrades device performance. In this work, we introduce a monolithic photolithography process for intrinsically stretchable complementary OFETs and circuits, with high yield, high resolution, and material versatility. This platform combines a directly photopatternable, solvent-resistant crosslinked dielectric/semiconductor interface, crosslinked high-mobility polymer-semiconductor blends, and self-aligned encapsulation that also serves as an etch mask. It patterns multiple p- and n-type polymer semiconductors, achieving a record density of 55,000 OFETs per cm2, 2 μm resolution, and 5 V operation voltages. We fabricated stretchable complementary inverters and 3.3 kHz ring oscillators, the first stretchable complementary OFET oscillators above 1 kHz and >60× faster than state-of-the-art processes, providing a scalable foundation for skin-like electronics.
    DOI:  https://doi.org/10.1016/j.device.2026.101204
  9. ACS Appl Bio Mater. 2026 Sep 10.
    Biocompatible Microscale DNA Hydrogels with Programmable Swelling and Sequence-Specific Dissolution.
    Corinna Torabi, Takayuki Suzuki, Emily Helm, Harrison Khoo, Sophie Tanenbaum, Rebecca Schulman, Soojung Claire Hur.
      Stimulus-responsive DNA hydrogels with swelling capabilities are a promising class of materials for biomedical applications such as drug delivery and biosensing. However, translation of these systems to microscale applications requires fabrication methods that are both biocompatible and material-efficient, while enabling precise control over stimulus-induced swelling and its impact on molecular transport. Here, we present a biocompatible fabrication and characterization platform for microscale DNA-hydrogels (μSDs) with tunable isotropic swelling and dissolving properties. Our approach includes a biocompatible, material-efficient fabrication workflow that conserves valuable DNA reagents by minimizing dead volume and process loss. We then demonstrated modular control over isotropic swelling in μSDs, achieving up to a two-fold size increase through programmable DNA design parameters. We further established a quantitative reaction-diffusion workflow to estimate effective diffusivity and characterize swelling dependent transport of a DNA binding fluorescent probe in spherical μSDs. Finally, we demonstrate the dissolution of μSDs using a DNA strand and find that dissolution kinetics are governed by the rates of coupled strand-displacement reactions and diffusive transport. This platform enables programmable swelling and structural disassembly in μSDs. Swelling-induced network expansion further modulates transport of a DNA binding fluorescent probe within the μSD network, highlighting the potential of programmable structural remodeling for future biosensing, controlled release, and single-cell assay applications.
    Keywords:  DNA crosslinked hydrogels; droplet microfluidics; effective diffusivity; programmable swelling; sequence specific dissolution; stimulus responsive hydrogels; strand displacement
    DOI:  https://doi.org/10.1021/acsabm.6c01207
  10. Cell Syst. 2026 Sep 09. pii: S2405-4712(26)00197-3. [Epub ahead of print] 101715
    Let there be multifunctionality: Uncovering the dynamical zoo of the AC-DC genetic circuit.
    Smitha Maretvadakethope, Içvara Aor, Matthias M Fischer, Àngela Pantebre Pedrosa, Yolanda Schaerli, Ruben Perez-Carrasco.
      Gene regulatory networks (GRNs) govern many cell processes. While multistability and oscillations are common GRN dynamics, they are typically studied and engineered in isolation. Here, we challenge this separation using the AC-DC circuit, a minimal three-gene network that merges the classical toggle switch and repressilator. Using a thermodynamic formalism and Bayesian inference, we show that a single-inducer version of the circuit displays diverse multifunctional dynamics, including coexistence of oscillations and multistability. We explore robustness, classify emergent behaviors, and analyze critical slowing down. Remarkably, the AC-DC circuit can produce more than thirty topologically distinct bifurcation diagrams, results that challenge the classical view that network topology rigidly constrains dynamical outcomes. This flexibility enables synthetic capabilities coupling hysteresis with oscillations, criticality, and reversibility. By uncovering the potential of minimal genetic circuits and outlining design principles for their implementation, this work opens directions for harnessing emergent complexity using the basic building blocks of life. A record of this paper's transparent peer review process is included in the supplemental information.
    Keywords:  bifurcation diagrams; cell decision; dynamical systems; gene regulatory networks; oscillations; systems biology
    DOI:  https://doi.org/10.1016/j.cels.2026.101715
  11. Nature. 2026 Sep;657(8131): 562-564
    Probing the proteome at cellular scale.
    Michael Eisenstein.
      
    Keywords:  Biological techniques; Cell biology; Proteomics; Technology
    DOI:  https://doi.org/10.1038/d41586-026-02805-w
  12. Front Bioeng Biotechnol. 2026 ;14 1895558
    Biomaterials in organoid research: current state and future directions.
    Laura Klasen, Ramin Nasehi, Lennart Selzener, Laura De Laporte.
      Organoid research has fundamentally reshaped in vitro approaches to modeling disease, drug response, and developmental processes. While the potential is great, the technology is limited by reproducibility and physiological accuracy challenges that arise partly from the shortcomings in extracellular matrix mimicking biomaterials that influence morphogenesis, differentiation, and functionality. In recent years, biomaterials for organoid systems have developed from biologically derived but poorly defined matrices toward tunable, dynamic, and modular systems that allow for precise control and better reproducibility of the microenvironment. This Mini-Review summarizes recent advances, with a focus on the last 3 years, in natural, synthetic, and hybrid biomaterials, highlighting engineered ECM-derived hydrogels, modified natural polymers, and synthetic systems with tunable viscoelasticity, degradability, and bioactive components. Furthermore, emerging trends and technological integrations, comprised of 3D and 4D bioprinting, granular hydrogels, organ-on-a-chip platforms, and AI-driven methods, will be discussed, which together support scalable and data-driven optimizations in organoid research. Summarized, these developments demonstrate the transition from a generic matrix-based culture toward engineered, tunable, and dynamic microenvironments, demonstrating biomaterial design as a fundamental element for next-generation organoid systems.
    Keywords:  biochemical cues; biomaterials; biophysical cues; natural matrices; organoids; synthetic matrices; technological advances
    DOI:  https://doi.org/10.3389/fbioe.2026.1895558
  13. Nat Commun. 2026 Aug 12. pii: 9682. [Epub ahead of print]17(1):
    Tailored living mycelium macerate for reproducible flexible actuators.
    Rui Nie, Baoyuan Li, Luxuan Li, Guangyao Hou, Yikai Gao, Xiaonan Wang, Yan Huang, Mei Zhu, Xiaoman Liu, Xin Huang.
      The integration of living attributes, such as self-renewal and responsiveness, into structural materials remains a fundamental challenge, as they typically preclude the mechanical robustness required for practical applications. Here, we report a fungal-based maceration tailored strategy to create living mycelium materials with exceptional mechanical properties and programmable humidity responsiveness. The developed materials demonstrate wide-range adjustable tensile performance, achieving 11 ~ 349% elongation and 0.1 ~ 18.0 MJ·m-3 toughness, the highest values reported among flexible mycelium materials. Through multiscale characterization from microstructural to molecular levels, we revealed the hygroscopic deformation mechanism of Janus mycelium macerates which arises from asymmetric hygromechanics and entropy-driven reorganization. Crucially, these materials retain their living functionalities, enabling reversible dormancy-regeneration cycles in 1 year and inheritable Janus structure along with self-renewal of performance. Moreover, we demonstrate their ability to convert environmental humidity fluctuations into quantifiable electrical signals, highlighting their potential as biohybrid environmental sensors and interactive platforms. This interdisciplinary study represents an integrative paradigm in living material design, and exhibits substantial potential for future sustainable and intelligent applications at the intersection of living mycelium materials and ecologically sustainable devices.
    DOI:  https://doi.org/10.1038/s41467-026-76623-z
  14. Nat Mater. 2026 Sep 08.
    A boost for CAR T cell therapy.
    Emily Fitzgerald, Marshall S Padilla, Michael J Mitchell.
      
    DOI:  https://doi.org/10.1038/s41563-026-02725-0
  15. Mater Horiz. 2026 Sep 07.
    Refractive-index-matched jammed microgel assemblies enable volumetric printing of porous hydrogel architectures.
    Minju Kim, Jiheon Kang, Sungchul Shin.
      Jammed microgels form porous hydrogel architectures in which packing-derived interstitial voids provide transport-accessible pathways while retaining the processability of soft granular matter. However, the same microgel-continuous phase interfaces scatter and redistribute projected light, complicating volumetric printing. Here, we develop refractive-index-matched jammed microgel assemblies by independently tuning the refractive indices of gelatin/acrylamide microgels and an immiscible silicone-oil continuous phase. Cooling-induced gelatin gelation stabilizes discrete microgels, whereas acrylamide photopolymerization integrates the packed particles within the irradiated regions. Matching the refractive indices of the microgels and surrounding oil confines the projected 405 nm light field and restores design-to-print fidelity to a level comparable to that of a homogeneous bulk-gel control despite the high density of particle interfaces. This optical improvement is achieved without eliminating the particle-assembled architecture. The printed constructs retain packing-derived interstitial porosity and can be transferred from the oil-containing printing state into an aqueous hydrogel state while maintaining their overall geometry and measurable mechanical integration. Across the size-varied formulations, assemblies containing larger microgels exhibit wider interstitial features and greater dye penetration, whereas those containing smaller microgels show more restricted dye penetration and greater rheological and compressive resistance. These findings establish independent refractive-index control of the microgel and continuous phases as a materials design strategy for reconciling the optical requirements of volumetric printing with the structural and functional heterogeneity of particle-assembled soft materials.
    DOI:  https://doi.org/10.1039/d6mh01527a
  16. Nat Mater. 2026 Sep 09.
    Molecular modifier aids melting of MOFs.
    Catriona Thomson, Ross S Forgan.
      
    DOI:  https://doi.org/10.1038/s41563-026-02738-9
  17. Mar Biotechnol (NY). 2026 Sep 10. pii: 154. [Epub ahead of print]28(5):
    A Non-Living, Microbe-Based Surface Coating Promotes Tubeworm and Coral Settlement.
    Morgan V Farrell, Laura Rix, Paul A O'Brien, Tiffany L Dunbar, Shivani Mahesh, Felicity Kuek, Nicholas J Shikuma.
      A major barrier to scaling marine restoration and aquaculture is the lack of reliable tools to induce invertebrate larvae to settle and metamorphose when and where needed. Although microbial cues are known to induce metamorphosis in many invertebrates, existing methods rely on natural biofilms that are variable, difficult to standardize, and unsuitable for large-scale deployment. Here we introduce ReefTiles, a non-living bacterial coating that preserves inductive activity from metamorphosis-stimulating marine bacteria in a stable, reproducible format. Using both tubeworm and coral larvae, we show that dried and inactivated bacterial films retain full settlement-inducing capacity, matching or exceeding live biofilms while eliminating concerns associated with releasing viable microbes into the environment. Viability assays confirm inactivation, and the coating adheres reliably to common substrate materials. Because ReefTiles can be manufactured and stored at scale and tailored to different inductive strains, they provide a practical microbe-based biotechnology for enhancing larval settlement in reef restoration, sustainable aquaculture, and engineered marine infrastructure.
    DOI:  https://doi.org/10.1007/s10126-026-10703-5
  18. mBio. 2026 Sep 09. e0113226
    Activation-independent capture of free fatty acids at the bacterial cell envelope by BrtB.
    Amaranta Kahn, Cristina I F Sousa, João P A Reis, David A Russo, Adriana Rego, Ricardo J C V Queirós, Marine Cuau, Julie A Z Zedler, Sandra A C Figueiredo, Paulo Oliveira, Pedro N Leão.
      Fatty acids (FAs) are key metabolites in living organisms, shaping membrane architecture, and helping cellular acclimatization to changing conditions. Bacteria synthesize FAs de novo but can also reclaim them from membrane lipids or uptake them from the environment, usually converting free fatty acids (FFAs) into activated FAs that can then be further metabolized. In cyanobacteria, it is the acyl-acyl carrier protein synthetase (Aas) that activates exogenous FFAs. However, the cyanobacterial enzyme BrtB was recently shown to esterify, in vitro, FFAs directly onto abundant chlorinated glycolipids (bartolosides), generating bartoloside fatty acid esters (B-FAs). Whether this chemistry operates in vivo, where it occurs, and what its implications are for cell physiology have remained unclear. Here, we show that in the cyanobacterium Synechocystis salina LEGE 06099, BrtB likely esterifies exogenous FFAs at or near the cell envelope without prior activation to generate B-FAs. We found that supplemented FFAs were converted into B-FAs within minutes. Unexpectedly, this response occurred with minimal changes in gene expression and little alteration of the extracellular proteome, consistent with a pathway already in place. Additionally, we observed that B-FAs can further be hydrolyzed into hydroxybartolosides, the levels of which increase in response to FA supply, suggesting a transient sequestration of FFA. These findings identify a specific activation-independent route for the incorporation of exogenous FFAs into cyanobacterial specialized metabolites, expanding the known repertoire of bacterial FA utilization.
    IMPORTANCE: Fatty acids (FAs) are essential building blocks of cell membranes and key metabolites in all living organisms. While bacteria synthesize FAs de novo, they can also incorporate exogenous FAs, saving the energetic cost of biosynthesis. Bacteria are generally thought to require their prior activation before they can be incorporated into metabolism. Here we show that a marine cyanobacterium bypasses this requirement through BrtB, which directly esterifies exogenous FAs onto specialized glycolipids in vivo without prior activation, likely at or near the cell envelope. This process occurs within minutes and is accompanied by minimal changes in gene expression, consistent with a pre-existing pathway. Our findings identify a specific activation-independent route for incorporation of exogenous FAs into cyanobacterial specialized metabolites and suggest that these glycolipids may transiently sequester FAs in response to environmental availability.
    Keywords:  cell envelope; cyanobacteria; fatty acid metabolism; glycolipids; natural products
    DOI:  https://doi.org/10.1128/mbio.01132-26
  19. Trends Biotechnol. 2026 Sep 09. pii: S0167-7799(26)00346-X. [Epub ahead of print]
    Engineering biosensors to enhance monoterpene indole alkaloid production in yeast.
    Maxence Holtz, Simon D'Oelsnitz, Cecília Castellví Domingo, Niklas G Madsen, Mars Yu Hong, Jonathan Asmund Arnesen, Aafke C A van Aalst, Samantha de Haan, Christopher K Weingarten, Ditte H Welner, Pamela A Silver, Yan Jessie Zhang, Michael K Jensen, Carlos G Acevedo-Rocha.
      Monoterpene indole alkaloids (MIAs) are medicinally valuable plant natural products, but their scarcity and structural complexity hinder conventional production. Microbial cell factories offer a sustainable alternative, although optimization of their long biosynthetic pathways is constrained by costly, low-throughput analytics. In this article, we evolved the promiscuous bacterial transcription factor RamR to detect five MIAs, obtaining sensitive and selective biosensor variants with EC50 values below 10 μM. We functionalized RamR in yeast and used it to screen a 188-gene overexpression library for improved strictosidine (STR) production, the common precursor for all MIAs. Biosensor fluorescence strongly correlated with HPLC measurements (R2 = 0.932), enabling identification of engineering targets that, when combined, increased STR titers more than threefold to over 220 mg/l. This RamR-based biosensing platform enables cost-effective screening and makes large biological design spaces experimentally accessible, accelerating strain and enzyme engineering for MIAs and other complex natural products.
    Keywords:  RamR; biosensor; directed evolution; metabolic engineering; monoterpene indole alkaloids; synthetic biology
    DOI:  https://doi.org/10.1016/j.tibtech.2026.08.011
  20. Phys Rev Lett. 2026 Aug 21. 137(8): 088301
    Curved Odd Elasticity.
    Yuan Zhou, Lazaros Tsaloukidis, Jack Binysh, Yuchao Chen, Nikta Fakhri, Corentin Coulais, Piotr Surówka.
      Living materials such as membranes, cytoskeletal assemblies, cell collectives, and tissues can often be described as active solids-materials that are energized from within, with elastic response about a well-defined reference configuration. These materials often live in complex and curved manifolds, yet most descriptions of active solids are flat. Here, we explore the interplay between curvature and nonreciprocal elasticity via a covariant effective theory on curved manifolds in combination with numerical simulations. We find that curvature spatially patterns activity, gaps the spectrum, modifies exceptional points, and introduces non-Hermitian defect modes. Together, these results establish a foundation for hydrodynamic and rheological models on curved manifolds, with direct implications for living matter and active metamaterials.
    DOI:  https://doi.org/10.1103/fhwd-lmgk
  21. Nature. 2026 Sep;657(8131): S14-S15
    Drug delivery gets subcellular.
    Katherine Bourzac.
      
    Keywords:  Cell biology; Therapeutics
    DOI:  https://doi.org/10.1038/d41586-026-02659-2
  22. iScience. 2026 Sep 18. 29(9): 117009
    Extracellular matrix composition and stiffness regulates progesterone responsiveness and decidualization.
    Danielle Klunk, Laura Homewood, Daniel Abebayehu.
      Endometrial disorders impact the uterine lining and can promote ectopic endometrial tissue growth. A key feature of endometrial disorders is unresponsiveness to hormonal treatments due to progesterone resistance. Because endometrial lesions are found within fibrotic extracellular matrix (ECM), we hypothesized that ECM stiffness and composition regulate progesterone responses. We used hydrogels to mimic physiological stiffnesses and examine how mechanical and biochemical ECM cues influence progesterone-induced differentiation (decidualization) in healthy fibroblasts. We determined that ECM ligands modulate decidualization, with laminin slowing secretory responses in favor of stabilizing upstream FOXO1 and WNT4 signaling, while fibronectin produces quicker but less stable differentiation. Stiff matrices override these ECM cues and inhibit decidualization across ligands. Furthermore, these findings mirror activity in endometriotic lesions, with lesions across the stiffest sites displaying greater fibronectin expression and lower decidualization. Altogether, these data demonstrate a role for the lesion microenvironment in the mechanism of inhibited decidualization and progesterone responses.
    Keywords:  ECM; endometrium; fibroblasts; matrix biology; progesterone responsiveness
    DOI:  https://doi.org/10.1016/j.isci.2026.117009
  23. Sci Adv. 2026 Sep 11. 12(37): eaee5415
    Robust cellular transformations of PET deconstruction products by import of glycol esters.
    Roman M Dickey, Esun Selvam, Erha Andini, Priyanka Nain, Dionisios G Vlachos, Aditya M Kunjapur.
      Efforts to transform polyethylene terephthalate (PET) deconstruction products using live cells have been limited by terephthalic acid (TPA) uptake. Here, we used an intracellular carboxylate reduction assay to show that apparent TPA uptake in E. coli cells that lack a dedicated TPA transporter sharply increases from pH 6 to 5. More importantly, we found that glycol ester deconstruction products, mono(2-hydroxyethyl) terephthalate (MHET) and bis(2-hydroxyethyl) terephthalate (BHET), unexpectedly each result in rapid pH-independent uptake. We exploited glycol ester uptake, along with deletion of 22 cellular oxidoreductases, to design intracellular hydrolysis routes for synthesis of upcycled reduction products from BHET at >90% yields and from real PET wastes after tandem catalytic glycolysis and cell-based valorization at >80% combined yields. Our work has important ramifications for PET utilization by cells and adds new perspectives on the evolution of the PETase/MHETase system.
    DOI:  https://doi.org/10.1126/sciadv.aee5415
  24. Nat Biomed Eng. 2026 Sep 11.
    Dense RNA motif modifications enable robust in vivo prime editing and enhance efficiencies of diverse editing systems.
    Xinlin Lei, Didi Chen, Kun Zhang, Xiyu Liu, Qiubing Chen, Yizhou Zhang, Ruijin Ji, Jicheng Zhu, Qingyi Zhang, Ying Zhang, Hao Yin.
      Prime editing holds promise for therapeutic applications. However, viral delivery of the prime editor presents challenges for clinical translation due to concerns regarding long-term expression. Meanwhile, systemic delivery using non-viral vectors has been limited by low efficiency, the need for repeated injections and reliance on doses that exceed clinically translatable levels. Here we develop engineered prime editing guide RNAs (pegRNAs) with densely modified RNA motifs and demonstrate their application for efficient in vivo prime editing. By systemically delivering the prime editor in RNA format via a single injection of lipid nanoparticles, we achieved nearly 70% editing efficiency in the bulk mouse liver, indicating successful editing of the majority of hepatocytes. Notably, a single injection at a clinically translatable lipid nanoparticle dose was sufficient to suppress target protein expression in vivo, resulting in a near 80-fold increase in editing efficiency compared with conventional end-modified pegRNAs. Furthermore, incorporating densely modified RNA motifs, including the widely used MS2 motif, proved broadly applicable across various RNA sequences and split RNA-guided genome editing platforms, resulting in up to an 11-fold increase in base editing efficiency. These findings present a generalizable approach for enhancing the therapeutic potential of prime editing and expanding the utility of RNA-based therapeutics.
    DOI:  https://doi.org/10.1038/s41551-026-01787-4
  25. Biomaterials. 2026 Aug 28. pii: S0142-9612(26)00610-1. [Epub ahead of print]338(Pt A): 124586
    Layer-by-layer nanoparticle outer polyelectrolyte impacts protein corona formation.
    Tamara G Dacoba, Simone A Douglas-Green, Bhuvna Murthy, Alfonso D Restrepo, Zavian Strom, Margaret Billingsley, Alexander D Stoneman, Mae Pryor, Paula T Hammond.
      Nanoparticles (NPs) can be engineered to achieve targeted delivery with strategies based on surface modifications. These include layer-by-layer (LbL) NPs, modular electrostatically assembled carriers with tunable surface properties altered by changes to the outer polyelectrolyte layer. Variations in these polymers dictate intracellular trafficking and biodistribution patterns. As NPs are administered, a layer of protein adsorbs to their surfaces, forming a protein corona that affects NP properties, alters biodistribution, and ultimately impacts therapeutic efficacy. We hypothesized that some differences in LbL NP performance are due, in part, to variations in the resulting protein coronas. To study them, we first optimized an ultrafiltration method to effectively isolate LbL NPs with their protein corona. Following incubation in conditioned media, anionic homopolypeptide outer layers, such as poly-l-aspartic acid (PLD) and poly-l-glutamic acid (PLE), and LbL NPs with the bioinert polymer poly(acrylic acid) (PAA) had the lowest amount of protein associated, lower than conventional PEG liposomes. While mass spectroscopy revealed changes in the protein composition among LbL NPs; albumin, alpha-2-macroglobulin, and apolipoprotein B were most abundant, with PLE and HA NPs presenting unique protein profiles. In vitro, pre-formed protein coronas reduced uptake in macrophages but increased uptake in ovarian cancer cells for certain LbL NPs, which were protein-dependent. In vivo, LbL NP outer layer influenced both serum half-life and biodistribution. Overall, this work highlights that LbL NPs can be designed to control protein corona formation and supports the idea that further understanding NP interactions with biological fluids is essential for designing clinically translatable NP platforms.
    DOI:  https://doi.org/10.1016/j.biomaterials.2026.124586
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