bims-enlima 2025-11-02 papers

bims-enlima

Biomed News

on Engineered living materials

Issue of 2025–11–02
37 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool

Photosynthetic Biomanufacturing in Mechanically Robust, 3D Printed Hydrogels.
Robust zwitterionic hydrogels enabled by consolidated supramolecular networks and spatially hierarchical structures.
Programming cellular condensates for living materials using an intrinsically disordered protein display platform.
Growing functional artificial cytoskeletons in the viscoelastic confinement of DNA synthetic cells.
Highly Reprocessable Diels-Alder Networks with Rapid Gelation for Enhanced Printability.
Additive Manufacturing of Molecular Architecture Encoded Stretchable Polyethylene Glycol Hydrogels and Elastomers.
High-Throughput Discovery of Ferrocene Mechanophores with Enhanced Reactivity and Network Toughening.
Alternating Electrochemical Redox-Cycling on Nanocomposite Biointerface for High-Efficiency Enzyme-Free Cell Detachment.
A dynamic biointerface in mussels mediated by a mechanoresponsive intermediate filament-based biopolymer.
Stress-hardening behaviour of biofilm streamers.
Engineering Escherichia coli for High-Yield Protoporphyrin IX Biosynthesis via Cytotoxicity Mitigation and Pathway Optimization.
Advances in the microbial biosynthesis of therapeutic terpenoids.
Closed-Loop Recyclable and Multifunctional Supramolecular Hydrogel from Reversible Ring-Opening Polymerization of Guanidine-Modified Thioctic Acid in Water.
Demonstration and technoeconomic analysis of dodecanol production from acetate using metabolically engineered Escherichia coli.
Small RNAs positively and negatively control transcription elongation through modulation of Rho utilization site accessibility.
Design of Light Driven Hole Bifurcating Proteins.
The mechanical response of vinculin.
Bioinspired synergistic texture and color modulation enabled by surface instability of cholesteric liquid crystal elastomer bilayers.
UNICORN: Towards universal cellular expression prediction with a multi-task learning framework.
Smart Healthcare Photonic Nanomaterials and Devices.
Two-Layer Droplet Arrays Enable Dynamic Manipulation of Cell Microenvironment During High-Throughput Bacterial Cultivation.
Cryobioprinted human tumor models with shelf-stable programmability.
Biocompatible Interpenetrating Network Hydrogels with Dually Cross-Linked Polyol.
Spatiotemporal Control of Liquid-Liquid Phase Separation for Advanced Biomanufacturing.
Natural language processing of gene descriptions for overrepresentation analysis with GeneTEA.
Mining extreme properties from a large metamaterial database.
Ultrasound-driven programmable artificial muscles.
PEG alternatives for RNA therapeutics.
Molecular 'glues' and 'bumpers' on receptors can bias signalling inside the cell.
Soft Ionic Materials: Design and Applications in Functional Electrochemical Systems.
Mechanism and Engineering Strategies of Sterol Homeostasis in Yeast.
The mevalonate pathway of isoprenoid biosynthesis supports metabolic flexibility in Mycobacterium marinum.
Dynamic Structural Organization of Biomolecular Condensates in Escherichia coli Cells.
Controlled Release of Dyes from Hydrogel Cargoes through pH and Magnetic Stimuli.
Breeding of yeast strains with intracellular amino acid accumulation for value-added alcoholic beverages.
Chromatin profiling identifies putative dual roles for H3K27me3 in regulating cell type-specific genes and transposable elements in choanoflagellates.
GotEnzymes2: expanding coverage of enzyme kinetics and thermal properties.

ACS Synth Biol. 2025 Oct 29.

Photosynthetic Biomanufacturing in Mechanically Robust, 3D Printed Hydrogels.

Jayce E Taylor, Kinsey Drake, Nhu Tong, Jada A Bezue, Alshakim Nelson, Shota Atsumi.

  Engineered living materials (ELMs) integrate synthetic polymers with engineered cells to create systems that sense, respond, and adapt to their environment. While promising as sustainable alternatives to traditional materials, ELMs remain underexplored for use with photoautotrophic organisms. In this study, we evaluate the viability of the cyanobacterium Synechococcus elongatus PCC 7942, which converts carbon dioxide into valuable chemicals using light energy, in three hydrogel matrices previously shown to support heterotrophic cells. S. elongatus remained viable and metabolically active only in a hydrogel formed from bovine serum albumin-conjugated acrylates. When engineered to produce 2,3-butanediol (23BDO), encapsulated cells generated 719 mg L-1 over four days. Incorporating cells increased the compressive modulus of the material, while accumulated 23BDO reduced it, indicating that bioproduction influences mechanical properties. Fluorescence imaging confirmed high viability and physical immobilization. These results establish that cyanobacteria-based ELMs can enable autotrophic chemical production while modulating material mechanics for sustainable applications.

Keywords:  biomaterials; cyanobacteria; engineered living materials; engineered living systems; metabolic engineering

DOI:  https://doi.org/10.1021/acssynbio.5c00366
Nat Commun. 2025 Oct 27. 16(1): 9454

Robust zwitterionic hydrogels enabled by consolidated supramolecular networks and spatially hierarchical structures.

Xingkui Guo, Lijie Zhang, Hao Zhuo, Chuyang Chen, Hang Yang, Tian Li, Haobo Qi, Wei Zhai.

Zwitterionic hydrogels have emerged as promising candidates for diverse applications, especially in epidermal electronics, due to their prominent hemocompatibility, superhydration, and nonfouling properties. However, their practical applications are often severely hindered by inadequate mechanical properties and limited functionalities. Here, we develop a mechanically robust zwitterionic hydrogel with an optimal combination of functions (RHOCF) by constructing a consolidated dynamic supramolecular framework and a spatially multiscale hierarchical structure. By finely introducing a reinforced entangled supramolecular network, along with hierarchical architectures across multiple length scales into the zwitterionic hydrogel system, we can engineer highly stiff and tough zwitterionic hydrogels that seamlessly integrate typically incompatible mechanical properties, including excellent stretchability, notable tensile strength, high fracture toughness, considerable stiffness, and great resilience. The RHOCF further integrates optical transparency, ionic conductivity, self-adhesion, and freezing tolerance, enabling conformal contact with dynamic, irregular surfaces for stable motion sensing and artifact-free electrophysiological signal acquisition.

DOI: https://doi.org/10.1038/s41467-025-64498-5
Proc Natl Acad Sci U S A. 2025 Nov 04. 122(44): e2510167122

Programming cellular condensates for living materials using an intrinsically disordered protein display platform.

Rong Chang, Hann X Tu, Hongyu Ma, Neel S Joshi.

  Self-organization underpins the emergence of complex structure in living systems but remains a major challenge for engineering synthetic multicellular materials. Here, we present intrinsically disordered protein display platform (iDP2), a generalizable platform for high-density display of intrinsically disordered proteins (IDPs) on the surface of Escherichia coli. iDP2 uses CsgF as a surface-tethered scaffold, enabling efficient fusion and presentation of protein domains that lack stable tertiary structure. Successful display selectively favors disordered sequences, which, when endowed with phase separation propensity, drive the formation of dynamic cellular condensates. Programming cells with orthogonal IDPs enables sequence-specific segregation of mixed populations, allowing the design of spatially organized living assemblies. The aggregation state of these condensates is dynamically tunable by environmental cues such as ionic strength, and temperature, with responses predictable from the known phase behavior of the displayed IDPs. Extrusion processing of condensates generates macroscale filaments that maintain structural integrity and population segregation. By linking protein sequence to emergent collective behaviors, iDP2 offers a programmable framework for rational control of cell-cell interactions. This approach establishes a foundation for engineering living materials with customizable viscoelastic properties, environmental responsiveness, and multicellular organization. More broadly, our work highlights the potential of disordered protein motifs as versatile tools for the design of adaptive, self-organizing biological systems.

Keywords:  cell surface display; intrinsically disordered protein; living materials; multicellular patterning

DOI:  https://doi.org/10.1073/pnas.2510167122
Nat Chem Eng. 2025 ;2(10): 627-639

Growing functional artificial cytoskeletons in the viscoelastic confinement of DNA synthetic cells.

Weixiang Chen, Siyu Song, Avik Samanta, Soumya Sethi, Christoph Drees, Michael Kappl, Hans-Jürgen Butt, Andreas Walther.

  Intracellular structures, such as cytoskeletons, form within a crowded cytoplasm with viscoelastic properties. While self-assembly in crowding is well studied, the effects of coupled viscoelastic environments remain elusive. Here we engineer all-DNA synthetic cells (SCs) with tunable viscoelastic interiors to investigate this phenomenon. We introduce facile DNA barcode engineering to selectively enrich DNA tiles with adjustable concentrations into SCs to form artificial cytoskeletons coupled to their interior. Distinct mechanistic differences in assembly occur compared with solution or simple crowding. Furthermore, we develop light, molecular and metabolic switches to direct structure formation and create self-sorted SC populations with distinct artificial cytoskeletons. These cytoskeletons strengthen SCs and support stable contacts with mammalian cells. By bridging molecular-scale DNA nanotube assembly with mesoscale condensate structures, our SCs provide a versatile platform to investigate self-assembly under viscoelastic confinement and to harness subcellular architectures for emerging applications.

Keywords:  Bioinspired materials; DNA nanotechnology; Self-assembly; Soft materials

DOI:  https://doi.org/10.1038/s44286-025-00289-5
ACS Appl Mater Interfaces. 2025 Oct 31.

Highly Reprocessable Diels-Alder Networks with Rapid Gelation for Enhanced Printability.

George Misiakos, Sandra Van Vlierberghe.

  Extrusion-based additive manufacturing of dynamic covalent polymer networks has faced longstanding challenges, preventing widespread adoption. Dynamic cross-linking via the thermoreversible Diels-Alder (DA) reaction has shown potential, however slow reaction rates resulting in poor viscosity control and thermal instability have posed significant constraints. Herein, we present a modular, scalable, solvent-free synthetic approach tailored to extrusion-based 3D printing. Linear oligomers densely functionalized with furan pendant groups are synthesized to accelerate postextrusion gelation. Through facile control of cross-linking density, networks with stiffnesses spanning from 2 to 200 MPa are obtained. Exceptional robustness to processing conditions is demonstrated via dynamic rheology, with networks undergoing 20 reprocessing cycles, marking a significant improvement for DA-based materials. Autonomous scratch healing at 20 °C is shown by a network combining high cross-linking density and chain mobility. Structures with mm-thin upright walls were printed using minimal or no support, marking an advancement in achievable features using purely dissociative DA-cross-linked networks, without viscosity-regulating additives. Fast gelation unlocks the trade-off between solidification rates and interlayer cross-linking, facilitating shape retention while mitigating mechanical anisotropy. The proposed approach establishes a pathway toward the scalable production of recyclable, tunable dynamic networks, providing a versatile platform for additive manufacturing, self-healing applications, and sustainable material development.

Keywords:  Diels−Alder reaction; additive manufacturing; covalent adaptable networks; extrusion; self-healing

DOI:  https://doi.org/10.1021/acsami.5c15489
Adv Mater. 2025 Oct 29. e12806

Additive Manufacturing of Molecular Architecture Encoded Stretchable Polyethylene Glycol Hydrogels and Elastomers.

Baiqiang Huang, Myoeum Kim, Pu Zhang, Emmanuel Oduro, Daniel A Rau, Li-Heng Cai.

  Polyethylene glycol (PEG) networks are widely used in biomedical applications and are emerging as solid-state polymer electrolytes for next-generation lithium batteries. Leveraging additive manufacturing technologies, such as digital light processing (DLP), PEG networks can be transformed into micro-architected metals and functional biomimetic vascular networks. However, developing stretchable PEG networks, let alone making them 3D printable, remains a fundamental challenge. Here, DLP printable, highly stretchable foldable bottlebrush PEG networks are reported. These networks are formed by rapid photopolymerization of low-cost commercial chemicals in ambient air. The bottlebrush architecture enables high molecular weight PEG network strands that do not crystallize and remain elastic without solvents at room temperature. Upon large deformation, the folded bottlebrush backbone unfolds to release stored length to enable extreme stretchability. The resulting hydrogels and elastomers exhibit tissue-like moduli ranging from ≈1 to ≈100 kPa and tensile breaking strains up to 1500%. The applications of bottlebrush PEG networks are demonstrated as matrices for highly stretchable and conductive solvent-free polymer electrolytes at room temperature (≈900% strain and 1.2 mS cm-1), as well as resins for DLP printing of complex architectures, cytocompatible organ-like geometries, functional devices, and multi-material structures with seamless interface integration. The developed photocurable bottlebrush PEG networks promise immediate applications in advanced (bio)manufacturing and beyond.

Keywords:  additive manufacturing; bottlebrush; polyethylene glycol; solid‐state polymer electrolytes; stretchable networks

DOI:  https://doi.org/10.1002/adma.202512806
ACS Cent Sci. 2025 Oct 22. 11(10): 1839-1851

High-Throughput Discovery of Ferrocene Mechanophores with Enhanced Reactivity and Network Toughening.

Ilia Kevlishvili, Jafer Vakil, David W Kastner, Xiao Huang, Stephen L Craig, Heather J Kulik.

Mechanophores are molecules that undergo chemical changes in response to mechanical force, offering unique opportunities in chemistry, materials science, and drug delivery. However, many potential mechanophores remain unexplored. For example, ferrocenes are attractive targets as mechanophores due to their combination of high thermal stability and mechanochemical lability. However, the mechanochemical potential of ferrocene derivatives remains dramatically underexplored despite the synthesis of thousands of structurally diverse complexes. Herein, we report the computational, machine learning guided discovery of synthesizable ferrocene mechanophores. We identify over one hundred potential target ferrocene mechanophores with wide-ranging mechanochemical activity and use data-driven computational screening to identify a select number of promising complexes. We highlight design principles to alter their mechanochemical activation, including regio-controlled transition state stabilization through bulky groups and a change in mechanism through noncovalent ligand-ligand interactions. The computational screening is validated experimentally both at the polymer strand level through sonication experiments and at the network level, where a computationally discovered ferrocene mechanophore cross-linker leads to greater than 4-fold enhancement in material tearing energy. This work establishes a generalizable framework for the high-throughput discovery and rational design of mechanophores and offers insights into structure-activity relationships in mechanically responsive materials.

DOI: https://doi.org/10.1021/acscentsci.5c00707
ACS Nano. 2025 Oct 29.

Alternating Electrochemical Redox-Cycling on Nanocomposite Biointerface for High-Efficiency Enzyme-Free Cell Detachment.

Caroline McCue, Wang Hee Lee, Bert Vandereydt, Domitille Avalle, Jimin Kang, Simon Rufer, Adel Atari, Fabian J Dickhardt, Michael Nitzsche, Sean Parks, Yuen-Yi Tseng, Kripa K Varanasi.

  The culture of anchorage-dependent cells is crucial in the biomedical industry, yet traditional dissociation methods, including enzymatic and mechanical techniques, often reduce cell viability and induce cellular stress, particularly in sensitive primary cell populations. These approaches are also resource-intensive, generate considerable biological waste, and lack compatibility with scalable or automated platforms. Here, we propose an enzyme-free and on-demand cell detachment strategy utilizing alternating electrochemical redox-cycling. This approach induces reversible morphological changes that promote cell detachment while maintaining high viability and stable proliferation. When applied to MG63 human osteosarcoma cells on a poly(3,4-ethylenedioxythiophene) polystyrenesulfonate nanocomposite biointerface, the application of voltage initiates redox-cycling, generating ion flux that disrupts cell adhesion and facilitates rounding within 5 min. Detachment efficiency increases from 1 to 95% at an optimal frequency of 0.05 Hz, with cell viability exceeding 90%, demonstrating the feasibility and effectiveness of this method. We introduce an efficient and enzyme-free solution for cell harvesting, which is compatible with automated cell culture and biomanufacturing workflows.

Keywords:  alternating redox-cycling; automated cell culture; conductive polymer nanocomposite; electroactive biointerface; enzyme-free cell detachment

DOI:  https://doi.org/10.1021/acsnano.5c09950
Nat Commun. 2025 Oct 28. 16(1): 9523

A dynamic biointerface in mussels mediated by a mechanoresponsive intermediate filament-based biopolymer.

Lucia Youssef, Jenaes Sivasundarampillai, Emily N P Prowse, E Deniz Eren, Franziska Jehle, Christopher Thibodeaux, Adam G Hendricks, Daniel J Jackson, Matthew J Harrington.

Mussels fabricate a distinctive biointerface that bridges their non-living biopolymeric byssus (used for anchoring in seashore habitats) with their soft-living tissue. Occurring in a region known as the byssus stem root, this biointerface is at once strong, yet also capable of on-demand release under apparent neurobiological control by the mussel, but this is not well understood. Here, we identify and sequence a previously unknown intermediate filament protein (MSP-1) that based on immunohistochemical staining and spectroscopic mapping comprises the surface of the stem root in direct contact with billions of motile cilia emerging from the living tissue. Further structural analysis indicates that MSP-1 is secreted as an α-helical coiled-coil but is mechanically converted subsequently to a β-sheet conformation. We posit that this mechanoresponsive conversion has a mechanical function in toughening the interface, but possibly also as a mechanosensory mechanism given its intimate contact with cilia in the living tissue.

DOI: https://doi.org/10.1038/s41467-025-64527-3
Nat Commun. 2025 Oct 28. 16(1): 9497

Stress-hardening behaviour of biofilm streamers.

Giovanni Savorana, Tommaso Redaelli, Domenico Truzzolillo, Luca Cipelletti, Eleonora Secchi.

Bacteria's ability to withstand mechanical challenges is enhanced in their biofilm lifestyle, where they are encased in a viscoelastic polymer matrix. Under fluid flow, biofilms can form as streamers - slender filaments tethered to solid surfaces and suspended in the flowing fluid. Streamers thrive in environments subjected to intense hydrodynamic stresses, such as medical devices and water filters, often resulting in catastrophic clogging. Their colonisation success may depend on a highly adaptable mechanical response to varying stress conditions, though the evidence and underlying mechanisms of this adaptation remain elusive. Here, we demonstrate that biofilm streamers exhibit a stress-hardening behaviour, with both differential elastic modulus and effective viscosity increasing linearly with external stress. This stress-hardening is consistent across biofilms with different matrix compositions, formed by various bacterial species, and under diverse growth conditions. We further demonstrate that this mechanical response originates from the properties of extracellular DNA (eDNA) molecules, which constitute the structural backbone of the streamers. In addition, our results identify extracellular RNA (eRNA) as a modulator of the matrix network, contributing to both the structure and rheological properties of the eDNA backbone. Our findings reveal an instantaneous, purely physical mechanism enabling streamers to adapt to hydrodynamic stresses. Given the ubiquity of extracellular nucleic acids (eNA) in biofilms, this discovery prompts a re-evaluation of their functional role in biofilm mechanics, with potential implications for biofilm structural integrity, ecological resilience, and colonisation dynamics.

DOI: https://doi.org/10.1038/s41467-025-64557-x
ACS Synth Biol. 2025 Oct 27.

Engineering Escherichia coli for High-Yield Protoporphyrin IX Biosynthesis via Cytotoxicity Mitigation and Pathway Optimization.

Peng Sun, Lin-Lin Qian, Wen-Liang Xie, Yao Jiang, Chun-Xiu Li, Jiang Pan, Jian-He Xu.

  Porphyrins are essential tetrapyrroles that play critical roles in biological electron-transfer and light-harvesting systems. As the universal precursor of heme and chlorophyll, protoporphyrin IX (PP IX) has transformative potential for fields as diverse as biomedicine, materials, food, and agriculture. However, large-scale microbial PP IX production is subject to challenges regarding cellular toxicity and regulation of tetrapyrrole biosynthesis. Herein, we report a synthetic-biology-driven Escherichia coli platform enabled by spatially resolved pathway optimization and cytotoxicity mitigation. By introducing a hyperactive 5-aminolevulinic acid synthase and rebalancing branch pathways via sRNA-based knockdown, we decoupled the PP IX synthesis from endogenous regulatory constraints. Integration of the MacAB-TolC efflux system reduced intracellular PP IX accumulation by 16%, synergistically enhancing extracellular productivity. PP IX titer values of 3.90 g/L and 65.0 mg/L/h productivity were achieved in a 5 L bioreactor, the highest ever reported. The engineered chassis exhibits metabolic plasticity, coproducing 0.24 g/L heme through dynamic pathway modifications. This work establishes a new paradigm for cytotoxic metabolite synthesis through spatiotemporal pathway governance, circumventing classical toxicity-productivity trade-offs. Our work establishes an efficient platform for microbial PP IX production. Furthermore, the engineered chassis developed here enables versatile applications in next-generation porphyrin biomanufacturing.

Keywords:  5-aminolevulinic acid; Escherichia coli; heme; metabolic engineering; protoporphyrin IX; synthetic sRNA

DOI:  https://doi.org/10.1021/acssynbio.5c00302
Curr Opin Biotechnol. 2025 Oct 28. pii: S0958-1669(25)00118-1. [Epub ahead of print]96 103374

Advances in the microbial biosynthesis of therapeutic terpenoids.

Peter H Winegar, Maria Ct Astolfi, Sara F Holm, Graham A Hudson, Jay D Keasling.

Terpenoid natural products and their derivatives exhibit bioactivity that is utilized in FDA-approved drugs and candidates for future drugs; however, the widespread utilization of terpenoids has been limited by complex, low-yielding native biosyntheses and chemical syntheses. Microbial total/semi-biosynthesis of natural and new-to-nature terpenoids from sustainable feedstocks is scalable and can achieve economically viable cost targets. Herein, this review describes foundational advances in synthetic biology and metabolic engineering as exemplified by efforts to biosynthesize prominent terpenoids (i.e. artemisinin, taxol, vinblastine, QS-21, and cyclopamine) in engineered microorganisms (e.g. Escherichia coli and Saccharomyces cerevisiae). Emerging methods that accelerate microbial biosynthesis campaigns (i.e. automation, machine learning, artificial intelligence, and combinatorial screening) are then discussed.

DOI: https://doi.org/10.1016/j.copbio.2025.103374
ACS Appl Mater Interfaces. 2025 Oct 28.

Closed-Loop Recyclable and Multifunctional Supramolecular Hydrogel from Reversible Ring-Opening Polymerization of Guanidine-Modified Thioctic Acid in Water.

Chang Liu, Tianyue Li, Shaoyu Chen, Da-Hui Qu.

  The development of multifunctional hydrogels that seamlessly integrate antibacterial activity, self-healing, and closed-loop recyclability is crucial for advanced sustainable functional materials. Herein, we present a supramolecular hydrogel prepared exclusively via an evaporation-induced ring-opening polymerization (ROP) of a guanidine-modified thioctic acid (GTA) monomer in water. Remarkably, the resulting supramolecular hydrogel, i.e., poly(GTA), can be fully depolymerized into a monomer through a catalyst-free ring-closing depolymerization (RCD) process in water, enabling efficient closed-loop recycling. The cationic, dynamic, and hygroscopic properties of the guanidine motif endow the poly(GTA) hydrogel with unique features, including intrinsic antibacterial activity against both Escherichia coli and Staphylococcus aureus, humidity-sensitive morphology transitions, rapid self-healing, and closed-loop recyclability. Notably, the poly(GTA) hydrogel exhibits exceptional ductility (up to 15000% strain) and high adhesion to biological tissue surfaces (>15 KPa), highlighting its potential for various interface applications, including biomedical fields. As a proof-of-concept study, this work demonstrates a sustainable and straightforward strategy for constructing recyclable, multifunctional supramolecular hydrogels from a single small molecule in water, offering a promising platform for sustainable antibacterial materials and future interface applications.

Keywords:  Closed-Loop Recyclability; Guanidine; Multifunctionality; Poly(disulfide)s; Reversible Polymerization in Water

DOI:  https://doi.org/10.1021/acsami.5c19237
Metab Eng. 2025 Oct 27. pii: S1096-7176(25)00162-4. [Epub ahead of print]

Demonstration and technoeconomic analysis of dodecanol production from acetate using metabolically engineered Escherichia coli.

Paul M Perkovich, Yoel R Cortés-Peña, Justin J Baerwald, Thomas H Graupmann, Theodore A Chavkin, Shivangi Mishra, William T Cordell, Victor M Zavala, Brian F Pfleger.

  In a circular bioeconomy, the one-way conversion of petroleum to chemicals and CO2 is replaced with processes that reduce CO2 to energy carriers and useful materials that are returned to CO2 upon combustion. A circular bioeconomy that relies on photosynthesis to generate sugars as the chief energy carrier and precursor to chemical building blocks has yet to overcome many recalcitrant aspects of plant-based photosynthesis, namely, high feedstock costs, arable land scarcity, food competition, and fertilizer overuse. Acetate is a potential sustainable energy carrier because it can be produced from CO2 either electrocatalytically or by acetogens via the Wood-Ljungdahl pathway. In this work, we conducted a metabolic engineering study of Escherichia coli's ability to convert acetate into dodecanol as a model oleochemical product. We performed techno-economic and life cycle analyses to determine break-even points with alternative fossil fuel-based strategies and identified critical process performance parameters for supporting an industrial acetate-based bioprocess. These analyses showed that oleochemical yield is the primary driver of minimum oleochemical selling price and carbon intensity. Therefore, to increase yield on acetate, we deleted the aceBAK operon, which facilitates funneling of acetate into biomass instead of product. We performed additional strain engineering to increase flux towards dodecanol and increase acetate uptake. Finally, we demonstrated increased yield in controlled bioreactors, improving from 13% of the maximum theoretical yield to 37%. Rigorous uncertainty analyses assuming a range of market conditions and future technological performances resulted in 88% and 37% of simulated scenarios having lower carbon intensities than fossil fuel-based routes and lower minimum selling prices than the market price.

Keywords:  Metabolic engineering; acetate; dodecanol; life cycle analysis; oleochemicals; techno-economic analysis

DOI:  https://doi.org/10.1016/j.ymben.2025.10.007
mBio. 2025 Oct 31. e0292125

Small RNAs positively and negatively control transcription elongation through modulation of Rho utilization site accessibility.

Kristen R Farley, Andrew K Buechler, Colleen M Bianco, Carin K Vanderpool.

  Bacteria use a multi-layered regulatory strategy to precisely and rapidly tune gene expression in response to environmental cues. Small RNAs (sRNAs) form an important layer of gene expression control and most act post-transcriptionally to control translation and stability of mRNAs. We have shown that at least five different sRNAs (RydC, CpxQ, ArrS, GcvB, and OxyS) in Escherichia coli regulate the cyclopropane fatty acid synthase (cfa) mRNA. These sRNAs bind at different sites in the long 5' untranslated region (UTR) of cfa mRNA, and previous work suggested that they modulate RNase E-dependent mRNA turnover. Rho-dependent transcription termination in the cfa 5'' UTR was demonstrated, leading us to hypothesize that the sRNAs might also regulate cfa transcription elongation. In this study, we find that a pyrimidine-rich region flanked by sRNA binding sites in the cfa 5' UTR is required for premature Rho-dependent termination. We discovered that sRNA-dependent regulation of cfa depends on Rho, and the activating sRNA RydC has only a minor effect on RNase E-mediated turnover of cfa mRNA. A stem-loop structure in the cfa 5' UTR sequesters the pyrimidine-rich region required for Rho-dependent termination. The repressing sRNA CpxQ binds to the 5' portion of the stem and increases Rho-dependent termination, whereas the activating sRNA RydC binds downstream of the stem and decreases termination. These results reveal the versatile mechanisms sRNAs use to regulate target gene expression at transcriptional and post-transcriptional levels and demonstrate that regulation by sRNAs in long UTRs can involve modulation of transcription elongation.IMPORTANCEBacteria respond to stress by rapidly regulating gene expression. Regulation can occur through the control of messenger RNA (mRNA) production (transcription elongation), stability of mRNAs, or translation of mRNAs. Bacteria can use small RNAs (sRNAs) to regulate gene expression at each of these steps, but we often do not understand how this works at a molecular level. In this study, we find that sRNAs in Escherichia coli regulate gene expression at the level of transcription elongation by promoting or inhibiting transcription termination by a protein called Rho. These results help us understand new molecular mechanisms of gene expression regulation in bacteria.

Keywords:  Hfq; RNase E; small RNA; termination

DOI:  https://doi.org/10.1128/mbio.02921-25
ACS Cent Sci. 2025 Oct 22. 11(10): 1911-1920

Design of Light Driven Hole Bifurcating Proteins.

Xiao Huang, Jonathon L Yuly, Peng Zhang, William F DeGrado, Michael J Therien, David N Beratan.

Electron bifurcation reactions divide electrons from two-electron donors into high- and low-energy pools by transporting charge on spatially separated low- and high-potential electron hopping pathways. Bifurcation delivers electrons at potentials that drive downstream reactions in photosynthesis, respiration, and biocatalysis. Recent theoretical studies have described the requirements for effective ground-state electron bifurcation. The aim of this study is to design synthetic bifurcation constructs that can be driven by light. We describe a strategy to bifurcate holes (oxidizing equivalents) efficiently with light, and we present an illustrative energy landscape that could support this design. The design focuses on the electrochemical potentials and distances between cofactors. The analysis finds that hole bifurcation may be driven efficiently with light, guiding the further development of bioinspired networks that bifurcate charge and deliver the charges with prescribed electrochemical potentials.

DOI: https://doi.org/10.1021/acscentsci.5c00803
Sci Adv. 2025 Oct 31. 11(44): eady6949

The mechanical response of vinculin.

Xuyao Liu, Jingzhun Liu, Yinan Wang, Mingxi Yao, Karen B Baker, Benjamin Klapholz, Nicholas H Brown, Benjamin T Goult, Jie Yan.

Vinculin is a mechanosensitive adaptor that links actin to cell-matrix and cell-cell adhesions. Known as a mechanoeffector, it is recruited to adhesion sites under force via mechanotransducers talin and α-catenin. Here, we examine vinculin's mechanical properties to assess its role as a mechanotransducer. We find that at physiological loading rates, vinculin domains unfold at forces of 5 to 15 pN and refold rapidly when forces drop to 1 pN. This behavior is reminiscent of force-dependent switches in talin and α-catenin, suggesting vinculin domains also function as molecular switches. Unfolding induces large extension changes up to 150 nm in steps of 20 to 30 nm. These findings reveal that vinculin exhibits a previously unrecognized mechanical response, with dynamic folding/unfolding under force acting as a buffering mechanism. Given its role as a scaffold for many proteins, this mechanosensitive behavior supports a model where vinculin functions directly as a mechanotransducer, recruiting binding partners in a force-dependent manner.

DOI: https://doi.org/10.1126/sciadv.ady6949
Sci Adv. 2025 Oct 31. 11(44): eaea9183

Bioinspired synergistic texture and color modulation enabled by surface instability of cholesteric liquid crystal elastomer bilayers.

Xiao Yang, Jay Sim, Wenbin Huang, Ruike Renee Zhao.

Certain cephalopods can dynamically camouflage by altering both skin texture and color to match their surroundings. Inspired by this capability, we present a cholesteric liquid crystal elastomer-liquid crystal elastomer (CLCE-LCE) bilayer capable of simultaneous, reversible modulation of surface texture and structural color through programmable wrinkling. By tuning the bilayer's fabrication parameters, on-demand wrinkle morphologies and color combinations are achieved. Spatially selective ultraviolet (UV) curing allows localized surface textures, while chemical patterning of the CLCE layer enables region-specific color responses, expanding the design space for multifunctional, spatially encoded optical materials. The CLCE-LCE bilayer enables dynamic thermal regulation by tuning light absorption through synergistically modulating surface morphology and color. Notably, this system achieves strain-dependent multistate encoding via multistep selective UV curing, revealing distinct visual content under different applied strains. This work establishes a versatile platform that merges surface instabilities with tunable structural coloration, advancing intelligent materials with programmable, strain-responsive surface and optical properties.

DOI: https://doi.org/10.1126/sciadv.aea9183
Nat Commun. 2025 Oct 27. 16(1): 9455

UNICORN: Towards universal cellular expression prediction with a multi-task learning framework.

Tianyu Liu, Tinglin Huang, Lijun Wang, Yingxin Lin, Rex Ying, Hongyu Zhao.

Sequence-to-function analysis is a challenging task in human genetics, especially in predicting cell-type-specific multi-omic phenotypes from biological sequences such as individualized gene expression. Here, we present UNICORN, a computational method with improved prediction performances than the existing methods. UNICORN takes the embeddings from biological sequences as well as external knowledge from pre-trained foundation models as inputs and optimizes the predictor with carefully-designed loss functions. We demonstrate that UNICORN outperforms the existing methods in both gene expression prediction and multi-omic phenotype prediction at the cellular level and the cell-type level, and it can also generate uncertainty scores of the predictions. Moreover, UNICORN is able to link personalized gene expression profiles with corresponding genome information. Finally, we show that UNICORN is capable of characterizing complex biological systems for different disease states or perturbations. Overall, embeddings from foundation models can facilitate the understanding of the role of biological sequences in the prediction task, and incorporating multi-omic information can enhance prediction performances.

DOI: https://doi.org/10.1038/s41467-025-64506-8
Adv Mater. 2025 Oct 28. e18886

Smart Healthcare Photonic Nanomaterials and Devices.

Molly M Stevens, John A Rogers, Sei Kwang Hahn.

DOI: https://doi.org/10.1002/adma.202518886
Small Methods. 2025 Oct 29. e01417

Two-Layer Droplet Arrays Enable Dynamic Manipulation of Cell Microenvironment During High-Throughput Bacterial Cultivation.

Bijing Xiong, Maximilian Breitfeld, Petra S Dittrich.

  Arrays of pico-to-microliter droplets, organized on a surface, enable chemical and biological workflows at high throughput. Here, a platform employing two-layer droplets is presented to enable flexible manipulation of the droplets' microenvironment for dynamic biological cultivation. Arrays of 6784 agarose droplets (≈2.0 nL per droplet) encapsulating and immobilizing bacterial cells are generated. After that, aqueous droplets (≈3.7 nL) with a defined composition are deposited atop to form a thin liquid layer surrounding the agarose droplets. Chemical exchange between the two layers is extremely fast (equilibrium within 15 s for fluorescein). Moreover, the aqueous layer can be removed, opening the possibility to extract substances from the agarose droplets. Indeed, repeated addition and aspiration of a buffer successfully remove dyes or drugs previously added to the agarose droplets. Therefore, antibiotic drug testing can be performed under both static and transient exposure profiles. The latter reveals that bacterial responses such as bacterial killing and resuscitation are both heterogeneous at the single-cell level. Last, it is exemplified how such droplet manipulation strategy can also be use in long-term experimentation, where medium replenishment, performed at 12-h intervals during a 72-h experiment, enables the cultivation of a slow-growing microorganism in nanoliter droplets.

Keywords:  antimicrobial susceptibility testing; droplet manipulation; high‐throughput screening; open microfluidics; persistence; slow‐growing microorganism

DOI:  https://doi.org/10.1002/smtd.202501417
Trends Biotechnol. 2025 Oct 29. pii: S0167-7799(25)00406-8. [Epub ahead of print]

Cryobioprinted human tumor models with shelf-stable programmability.

Maria V Monteiro, Carlos Ezio Garciamendez-Mijares, David Sebastián Rendon Ruiz, Mafalda S Borralho, Rui Vitorino, Iola F Duarte, Vítor M Gaspar, Yu Shrike Zhang, João F Mano.

  Cryobioprinting enables simultaneous fabrication and cryopreservation of tissue analogs, surpassing the limitations of print-to-use biofabrication approaches. However, cryopreservation of living constructs remains challenging, requiring optimal cryopreservation conditions tailored to specific cell types and hydrogel bioinks. To address this, we explored the formulation of a decellularized extracellular matrix (dECM)-based hydrogel bioink containing cryoprotective agents (CPAs) to generate shelf-ready tumor-stroma pancreatic cancer models. Combinatorial screening of CPAs led to the discovery of a novel melezitose-glycerol-dECM formulation that exhibited superior cryoprotective properties in both tumor and stroma compartments. Exometabolomics analysis revealed that cryopreserved constructs exhibited similar metabolic activity to nonfrozen counterparts 14 days post thawing. Cryobioprinted tumor-stroma models in dECM-CPA bioinks also exhibited increased cell viability post thawing and suitable features for in vitro drug screening. Thus, our optimized cryoprotective strategy opens new opportunities to potentially explore any type of tissue decellularized bioinks for cryobioprinting off-the-shelf living constructs for widespread drug screening and beyond.

Keywords:  3D in vitro models; bioink; cryobioprinting; cryoprotective agents; pancreatic cancer

DOI:  https://doi.org/10.1016/j.tibtech.2025.09.018
Polymers (Basel). 2025 Oct 13. pii: 2737. [Epub ahead of print]17(20):

Biocompatible Interpenetrating Network Hydrogels with Dually Cross-Linked Polyol.

Ulygbek B Tuleuov, Alexander L Kwiatkowski, Akerke T Kazhmuratova, Lyazzat Zh Zhaparova, Yermauyt Nassikhatuly, Miroslav Šlouf, Andrey V Shibaev, Viktor I Petrenko, Senentxu Lanceros-Méndez, Yerkeblan M Tazhbayev.

  Modern tissue regeneration strategies rely on soft biocompatible materials with adequate mechanical properties to support the growing tissues. Polymer hydrogels have been shown to be available for this purpose, as their mechanical properties can be controllably tuned. In this work, we introduce interpenetrating polymer networks (IPN) hydrogels with improved elasticity due to a dual cross-linking mechanism in one of the networks. The proposed hydrogels contain entangled polymer networks of covalently cross-linked poly(ethylene glycol) methacrylate/diacrylate (PEGMA/PEGDA) and poly(vinyl alcohol) (PVA) with two types of physical cross-links-microcrystallites and tannic acid (TA). Rheological measurements demonstrate the synergistic enhancement of the elastic modulus of the single PEGMA/PEGDA network just upon the addition of PVA, since the entanglements between the two components are formed. Moreover, the mechanical properties of IPNs can be independently tuned by varying the PEGMA/PEGDA ratio and the concentration of PVA. Subsequent freezing-thawing and immersion in the TA solution of IPN hydrogels further increase the elasticity because of the formation of the microcrystallites and OH-bonds with TA in the PVA network, as evidenced by X-ray diffraction and ATR FTIR-spectroscopy, respectively. Structural analysis by cryogenic scanning electron microscopy and light microscopy reveals a microphase-separated morphology of the hydrogels. It promotes extensive contact between PVA macromolecules, but nevertheless enables the formation of a 3D network. Such structural arrangement results in the enhanced mechanical performance of the proposed hydrogels, highlighting their potential use for tissue engineering.

Keywords:  hydrogels; interpenetrating networks; microcrystallites; poly(vinyl alcohol); rheology; tannic acid

DOI:  https://doi.org/10.3390/polym17202737
ACS Synth Biol. 2025 Oct 29.

Spatiotemporal Control of Liquid-Liquid Phase Separation for Advanced Biomanufacturing.

Yingying Li, Can Zeng, Xiaoye Lyu, Wei Tan, Wei Zhao.

  Liquid-liquid phase separation (LLPS) is a fundamental mechanism that governs the spatiotemporal organization of biomolecules and is implicated in multiple neurodegenerative diseases. Recently, emerging evidence suggests that LLPS also holds significant potential as a tool in biomanufacturing, enabling advanced metabolic engineering through the generation of responsive compartments both in vivo and in vitro. This review focuses on the spatiotemporal control of LLPS for biomanufacturing applications and highlights recent advances in its use to enhance catalytic efficiency, facilitate programmed bioreactions, sequester toxic components, and serve as biosensors. We also discuss the major challenges confronting the application of LLPS in biomanufacturing and propose future directions for the rational design of programmable and robust synthetic systems based on LLPS.

Keywords:  biomanufacturing; liquid−liquid phase separation; membraneless organelles; spatiotemporal control

DOI:  https://doi.org/10.1021/acssynbio.5c00655
Genome Biol. 2025 Oct 30. 26(1): 376

Natural language processing of gene descriptions for overrepresentation analysis with GeneTEA.

Isabella A Boyle, Nayeem Akram Aquib, Mustafa Kocak, Randy Creasi, Philip Montgomery, Catarina D Campbell, Joshua M Dempster.

  Overrepresentation analysis is used to identify biological enrichment in a list of genes. Here, we introduce GeneTEA, a model that ingests free-text gene descriptions and incorporates natural language processing methods to learn a sparse gene-by-term embedding, which can be treated as a de novo gene set database. In benchmarks against existing overrepresentation analysis tools, only GeneTEA properly controls false discovery while consistently surfacing the most relevant biology, doing so with less redundancy. We show that the same approach can be applied to other organisms' genomes or compounds. Furthermore, we provide an interactive app and API for the trained GeneTEA model.

Keywords:  Gene sets; Natural language processing; Overrepresentation analysis

DOI:  https://doi.org/10.1186/s13059-025-03844-8
Nat Commun. 2025 Oct 31. 16(1): 9648

Mining extreme properties from a large metamaterial database.

Jiaxin Chen, Zhuoyi Wei, Xiaoyujie Xiao, Kai Wei, Xujing Yang, Zhaoliang Qu, Daining Fang.

Truss metamaterials exhibit a wide range of properties due to their unique node-strut architectures, which are artificially engineered through a delicate design process. However, their advanced applications are presently constrained by limited architectures and property ranges. Here, we propose a framework that systematically encodes architectural topologies and generates a comprehensive architecture-property database of over 1.8 million truss metamaterials. This database reveals numerous architectures with extreme properties, including Young's moduli near the Voigt bound, programmable Poisson's ratios from extremely negative to positive, and exceptional isotropic bi-mode. Moreover, we introduce the concept of mechanical isomerism. This mechanical isomerism uncovers the underlying mapping from symmetric and asymmetric architectures to extreme properties through the study of architectural variations. Our findings bridge theoretical design and engineering requirements in mining extreme properties from truss metamaterials, further enabling data-driven design, shape optimization, and advanced manufacturing.

DOI: https://doi.org/10.1038/s41467-025-64745-9
Nature. 2025 Oct;646(8087): 1096-1104

Ultrasound-driven programmable artificial muscles.

Zhan Shi, Zhiyuan Zhang, Justus Schnermann, Stephan C F Neuhauss, Nitesh Nama, Raphael Wittkowski, Daniel Ahmed.

Muscular systems1, the fundamental components of mobility in animals, have sparked innovations across technological and medical fields2,3. Yet artificial muscles suffer from dynamic programmability, scalability and responsiveness owing to complex actuation mechanisms and demanding material requirements. Here we introduce a design paradigm for artificial muscles, utilizing more than 10,000 microbubbles with targeted ultrasound activation. These microbubbles are engineered with precise dimensions that correspond to distinct resonance frequencies. When stimulated by a sweeping-frequency ultrasound, microbubble arrays in the artificial muscle undergo selective oscillations and generate distributed point thrusts, enabling the muscle to achieve programmable deformation with remarkable attributes: a high compactness of approximately 3,000 microbubbles per mm2, a low weight of 0.047 mg mm-2, a substantial force intensity of approximately 7.6 μN mm-2 and fast response (sub-100 ms during gripping). Moreover, they offer good scalability (from micrometre to centimetre scale), exceptional compliance and many degrees of freedom. We support our approach with a theoretical model and demonstrate applications spanning flexible organism manipulation, conformable robotic skins for adding mobility to static objects and conformally attaching to ex vivo porcine organs, and biomimetic stingraybots for propulsion within ex vivo biological environments. The customizable artificial muscles could offer both immediate and long-term impact on soft robotics, wearable technologies, haptics and biomedical instrumentation.

DOI: https://doi.org/10.1038/s41586-025-09650-3
Nat Mater. 2025 Nov;24(11): 1665

PEG alternatives for RNA therapeutics.

DOI: https://doi.org/10.1038/s41563-025-02408-2
Nature. 2025 Oct 29.

Molecular 'glues' and 'bumpers' on receptors can bias signalling inside the cell.



Keywords:  Chemical biology; Drug discovery

DOI:  https://doi.org/10.1038/d41586-025-03461-2
JACS Au. 2025 Oct 27. 5(10): 4655-4668

Soft Ionic Materials: Design and Applications in Functional Electrochemical Systems.

Hyeon Woo Yang, Daniel Sanghyun Cho, Juyoung Kang, Ji Hye Han, Yong Min Kim, Hong Chul Moon.

  By integrating the rapid ionic transport of ionic liquids with the structural integrity of polymers, ionogels achieve high conductivity, mechanical flexibility, and environmental stability. These attributes position them as promising solid-state electrolytes for soft electronics. Recent molecular innovations have yielded ionogels with remarkable stretchability, toughness, and multifunctionality, broadening their scope of applications. This Perspective highlights molecular-level strategies, such as copolymer design and dynamic cross-linking via ionic or supramolecular interactions, that tailor polymer-ion interactions and network dynamics. We then discuss how these strategies regulate ionicity, diffusivity, and segmental mobility. These microscopic processes ultimately determine macroscopic transport properties and enable advanced devices such as strain sensors, electrochromic supercapacitors, thermoelectric generators, and triboelectric nanogenerators. Finally, by integrating molecular design with mechanistic insight, we provide a forward-looking framework for developing scalable, robust, and adaptive ionogels that underpin next-generation ionotronic systems.

Keywords:  ionogels; ionotronics; molecular design strategies; polymer−ion interactions; soft electronics

DOI:  https://doi.org/10.1021/jacsau.5c01060
ACS Synth Biol. 2025 Oct 30.

Mechanism and Engineering Strategies of Sterol Homeostasis in Yeast.

Mengxuan Li, Hongwei Yu, Lidan Ye.

  Sterol homeostasis in yeast is governed by a complex and highly coordinated regulatory network that integrates transcriptional, post-translational, and subcellular mechanisms. These include modulation of gene expression, targeted degradation of biosynthetic enzymes, dynamic conversion of sterols into storage forms, and precise control of sterol trafficking, uptake, and secretion. Disruption of sterol homeostasis not only represents a major bottleneck limiting sustainable sterol overproduction, but also significantly impacts terpenoid biosynthesis. This review summarizes current knowledge of sterol homeostasis regulatory mechanisms in yeast, and introduces representative metabolic engineering strategies targeting key molecular players to maintain sterol homeostasis, highlighting their applications in sterol and terpenoid production. Additionally, we discuss the remaining challenges and propose future directions to overcome metabolic flux limitations and cytotoxicity constraints in yeast-based sterol production platforms.

Keywords:  metabolic engineering; sterol biosynthesis; sterol homeostasis; synthetic biology; terpenoid biosynthesis; yeast

DOI:  https://doi.org/10.1021/acssynbio.5c00508
J Bacteriol. 2025 Oct 30. e0028725

The mevalonate pathway of isoprenoid biosynthesis supports metabolic flexibility in Mycobacterium marinum.

Christine M Qabar, Edward E K Baidoo, Emine Akyuz Turumtay, Tariq M Qayum, Jay D Keasling, Cressida A Madigan, Daniel A Portnoy, Jeffery S Cox.

  Isoprenoids are a diverse class of natural products that are essential in all domains of life. Most bacteria synthesize isoprenoids through either the methylerythritol phosphate (MEP) pathway or the mevalonate (MEV) pathway, while a small subset encodes both pathways, including the pathogen Mycobacterium marinum (Mm). It is unclear whether the MEV pathway is functional in Mm, or why Mm encodes seemingly redundant metabolic pathways. Here, we show that the MEP pathway is essential in Mm, while the MEV pathway is dispensable in culture, with the ΔMEV mutant having no growth defect in axenic culture but a competitive growth defect compared to WT Mm. We found that the MEV pathway does not play a role in ex vivo or in vivo acute infection but does play a role in survival of peroxide stress. Metabolite profiling revealed that modulation of the MEV pathway causes compensatory changes in the concentration of MEP intermediates DOXP and CDP-ME, suggesting that the MEV pathway is functional and that the pathways interact at the metabolic level. Finally, the MEV pathway is upregulated early in the shift down to hypoxia, suggesting that it may provide metabolic flexibility to this bacterium. Interestingly, we found that our complemented strains, which vary in copy number of the polyprenyl synthetase idsB2, responded differently to peroxide and UV stresses, suggesting a role for this gene as a determinant of downstream prenyl phosphate metabolism. Together, these findings suggest that MEV may serve as an anaplerotic pathway to make isoprenoids under stress conditions.IMPORTANCEOrganisms from all domains of life utilize isoprenoids to carry out thousands of critical and auxiliary cellular processes, including signaling, maintaining membrane integrity, stress response, and host-pathogen interactions. The common precursor of all isoprenoids is synthesized via one of two biosynthetic pathways. Importantly, some bacteria encode both pathways, including M. marinum. We found that only one pathway is essential in M. marinum, while the nonessential pathway may confer metabolic flexibility to help the bacterium better adapt to various environmental conditions. We also found that the polyprenyl synthetase IdsB2 plays an important role in driving such phenotypes. Further, we demonstrate metabolic interplay between both functional pathways. These insights represent the first characterization of isoprenoid biosynthesis in dual pathway-encoding mycobacteria.

Keywords:  Mycobacterium marinum; diversity; isoprenoid; metabolism; methylerithritol; mevalonate; mycobacteria; terpene; terpenoid

DOI:  https://doi.org/10.1128/jb.00287-25
JACS Au. 2025 Oct 27. 5(10): 4728-4739

Dynamic Structural Organization of Biomolecular Condensates in Escherichia coli Cells.

Han Zu, Fang Pan, Heng-Li Fan, Zhi-Gang Qian, Xiao-Xia Xia.

  Hierarchical structures of biomolecular condensates in living cells are essential for cellular functions, particularly in orchestrating complex reactions through synergistic cooperation. However, our understanding of these structures remains limited, because controlling the hierarchical structures of condensates in living cells can be difficult. Here we create an artificial condensate system in model prokaryotic Escherichia coli cells via coexpressing two distinct intrinsically disordered proteins. By modulating the homotypic and heterotypic interactions between the two proteins, condensates with differential structural organization (cophase and multiphase separation) were successfully constructed and dynamically controlled via physical or chemical cues from the environments. In vitro reconstitutions further supported the underlying physicochemical principles of dynamic condensate organization. This study not only deepens our understanding of the structural organization of biomolecular condensates but also provides a useful strategy for dynamic regulation of synthetic condensates in living cells.

Keywords:  Escherichia coli; biomolecular condensates; dynamic regulation; synthetic biology

DOI:  https://doi.org/10.1021/jacsau.5c00600
Langmuir. 2025 Oct 27.

Controlled Release of Dyes from Hydrogel Cargoes through pH and Magnetic Stimuli.

Utsab Banerjee, Sayan Ganguly, Xiaowu Shirley Tang, Sushanta K Mitra.

Stimuli-responsive biomaterials capable of controlled, on-demand release are vital for next-generation therapeutic delivery. We present a dual-responsive hydrogel platform for the controlled release of dyes from hydrogel cargoes, regulated by both pH and magnetic stimuli. By integrating magneto-responsive sodium alginate hydrogels with ferrofluid, we engineer smart hydrogel cargoes capable of responding to physiological cues as well as to on-demand external triggers. In this work, we utilize the liquid-liquid encapsulation method to generate Rhodamine B dye-loaded hydrogel-based cargoes. Our system enables not only passive, pH-driven diffusion but also active, magnetically enhanced release, demonstrating for the first time dual-mode modulation of release profiles from encapsulated hydrogels within protective oil-based droplets. Upon external magnetic activation, hydrogel cargoes are extracted from their encapsulation and immersed in various aqueous environments, where their release kinetics are finely tuned by both pH-dependent swelling/shrinking and magnetic field-induced structural changes. We found that the incorporation of magnetic actuation significantly increases the effective diffusion coefficient (∼ 10-9 m2/s) as compared to that for the pH-assisted release (∼10-10 m2/s) of Rhodamine B from the hydrogel. This approach provides spatiotemporal control over release behavior, paving the way for advanced, remotely controllable strategies in targeted drug delivery, minimally invasive therapeutics, and adaptive biomaterials. Our findings highlight the transformative potential of multistimuli-responsive hydrogels as a versatile platform for next-generation biomedical applications.

DOI: https://doi.org/10.1021/acs.langmuir.5c04499
FEMS Yeast Res. 2025 Oct 29. pii: foaf065. [Epub ahead of print]

Breeding of yeast strains with intracellular amino acid accumulation for value-added alcoholic beverages.

Shota Isogai, Akira Nishimura, Hiroshi Takagi.

  The yeast Saccharomyces cerevisiae converts amino acids into volatile compounds with fruity and floral aromas during fermentation. These amino acid-derived aroma compounds play a critical role in defining the taste and flavor of alcoholic beverages such as sake, beer, and wine. The productivity of amino acid-derived aroma compounds depends on the intracellular availability of their precursor amino acids. Therefore, breeding yeast strains that accumulate amino acids provides a practical approach to developing alcoholic beverages with more unique and attractive sensory characteristics. In this minireview, we describe the isolation of yeast strains that overproduce branched-chain amino acids and phenylalanine, obtained through conventional mutagenesis of industrial brewing yeasts. We also discuss the mechanisms responsible for the increased production of these amino acids in the mutant strains, including altered feedback regulation and transcriptional control of key enzymes involved in their biosynthesis. In addition, we briefly introduce a plasmid-free genome editing system that enables precise modification of metabolic pathways without the integration of foreign DNA, allowing the construction of strains that are not classified as genetically modified organisms. This method represents a promising tool that allows flexible and fine-tuned engineering of yeast metabolic pathways, including the development of strains with tailored aroma profiles.

Keywords:   Saccharomyces cerevisiae ; Alcoholic beverage; Conventional mutagenesis; Feedback inhibition; Functional amino acids

DOI:  https://doi.org/10.1093/femsyr/foaf065
Nat Commun. 2025 Oct 29. 16(1): 9549

Chromatin profiling identifies putative dual roles for H3K27me3 in regulating cell type-specific genes and transposable elements in choanoflagellates.

James M Gahan, Lily W Helfrich, Laura A Wetzel, Natarajan V Bhanu, Zuo-Fei Yuan, Benjamin A Garcia, Robert J Klose, Alex de Mendoza, David S Booth.

Chromatin-based mechanisms contribute to the exquisite regulation of gene expression during animal development. But how those mechanisms evolved remains elusive. Here we investigate chromatin regulatory features in the closest relatives of animals, choanoflagellates. In a model choanoflagellate Salpingoeca rosetta, we compare chromatin accessibility and histone modifications to gene expression. Accessible genomic regions in S. rosetta primarily correspond to gene promoters, and we find no evidence of distal gene regulatory elements that resemble enhancers deployed to regulate developmental genes in animals. Remarkably, the histone modification H3K27me3 decorates genes with cell type-specific expression, revealing a functional similarity in S. rosetta and animals. Additionally, H3K27me3 marks LTR retrotransposons, retaining a potential ancestral role in regulating these elements. We further uncover a putative bivalent chromatin state at cell type-specific genes that consists of H3K27me3 and H3K4me1. Together, these data support the emergence of gene-associated histone modification states that underpin development before the evolution of animal multicellularity.

DOI: https://doi.org/10.1038/s41467-025-64570-0
Nucleic Acids Res. 2025 Oct 31. pii: gkaf1053. [Epub ahead of print]

GotEnzymes2: expanding coverage of enzyme kinetics and thermal properties.

Bingxue Lyu, Ke Wu, Yuanyuan Huang, Mihail Anton, Xiongwen Li, Sandra Viknander, Danish Anwer, Yunfeng Yang, Diannan Lu, Eduard Kerkhoven, Aleksej Zelezniak, Dan Gao, Yu Chen, Feiran Li.

Enzyme kinetics are fundamental for understanding metabolism, yet experimentally measured parameters remain scarce. To address this gap, we introduce GotEnzymes2, a substantially expanded resource covering 10 765 species, 7.3 million enzymes, and 59.6 million unique entries. Compared with the first version, GotEnzymes2 now integrates both catalytic and thermal parameters, enabling unified predictions of kcat, Km,kcat/Km, optimal temperature, and melting temperature. This expansion markedly broadens species and enzyme coverage, creating the most comprehensive database of enzyme kinetic and stability parameters to date. To construct the resource, we systematically benchmarked state-of-the-art models for catalytic and thermal parameter prediction, and incorporated the best-performing strategies to ensure accuracy and generalizability. Altogether, GotEnzymes2 provides the community with a powerful resource for data-driven enzyme discovery, design, and engineering, with broad applications in systems biology, metabolic engineering, and synthetic biology. GotEnzymes2 is publicly accessible at https://metabolicatlas.org/gotenzymes.

DOI: https://doi.org/10.1093/nar/gkaf1053