bims-enlima 2025-02-16 papers

bims-enlima

Biomed News

on Engineered living materials

Issue of 2025–02–16
37 papers selected by
Rahul Kumar, Tallinna Tehnikaülikool

Strategies to Expand the Genetic Code of Mammalian Cells.
A molecular proximity sensor based on an engineered, dual-component guide RNA.
Production of recombinant coiled coil silk proteins for materials synthesis.
Synthetic biomolecular condensates enhance translation from a target mRNA in living cells.
Chemical degradation as an enabling pathway to polymersome functionalization.
Holographic tomographic volumetric additive manufacturing.
Host-guest chemistry on living cells enabling recyclable photobiocatalytic cascade.
Engineered immunological niche directs therapeutic development in models of progressive multiple sclerosis.
Living material-derived intelligent micro/nanorobots.
De Novo Production of 1,6-Hexanediol and 1,6-Hexamethylenediamine from Glucose by Metabolic Engineered Escherichia coli.
Optogenetics with Atomic Precision─A Comprehensive Review of Optical Control of Protein Function through Genetic Code Expansion.
Biopolymeric Gels: Advancements in Sustainable Multifunctional Materials.
Spontaneous Self-Organized Order Emerging From Intrinsically Disordered Protein Polymers.
Information Processing in Biochemical Networks.
Modular plasmid design for autonomous multi-protein expression in Escherichia coli.
Geometric modeling of knitted fabrics.
DNA-encoded dynamic hydrogels for 3D bioprinted cartilage organoids.
Spatial population dynamics of bacterial colonies with social antibiotic resistance.
Distinct Acyl Carrier Protein Docking Sites Help Mediate the Opposite Stereoselectivities of A- and B-type Modular Polyketide Synthase Ketoreductases.
Dynamic global acetylation remodeling during the yeast heat shock response.
Localized assembly in biological activity: Origin of life and future of nanoarchitectonics.
High-Resolution Self-Assembly of Functional Materials and Microscale Devices via Selective Plasma Induced Surface Energy Programming.
Metabolic division engineering of Escherichia coli consortia for de novo biosynthesis of flavonoids and flavonoid glycosides.
Boronic Acid-Linked Apo-Zinc Finger Protein for Ubiquitin Delivery in Live Cells.
Controllable Polymerization of Inorganic Ionic Oligomers for Precise Nanostructural Construction in Materials.
Fully addressable designer superstructures assembled from one single modular DNA origami.
Dynamic and Reversible Tuning of Hydrogel Viscoelasticity by Transient Polymer Interactions for Controlling Cell Adhesion.
Functional Biomaterials Derived from Protein Liquid-Liquid Phase Separation and Liquid-to-Solid Transition.
Bacteria encode post-mortem protein catabolism that enables altruistic nutrient recycling.
A bacterial antiviral system detects and directly fights against infection.
Tumor-Targeted Delivery of PD-1-Displaying Bacteriophages by Escherichia coli for Adjuvant Treatment of Colorectal Cancer.
Molecularly Functionalized Biomass Hydrogels for Sustainable Atmospheric Water Harvesting.
Hybrid mechanical metamaterials: Advances of multi-functional mechanical metamaterials with simultaneous static and dynamic properties.
Turbulent mixing controls fixation of growing antagonistic populations.
Injectable hyaluronic acid-based hydrogel niches to create localized and time-controlled therapy delivery.
Polyacrylamide-Based Hydrogel with Biocompatibility and Tunable Stiffness for Three-Dimensional Cell Culture.
Conformational ensembles reveal the origins of serine protease catalysis.

Chem Rev. 2025 Feb 12.

Strategies to Expand the Genetic Code of Mammalian Cells.

Arianna O Osgood, Zeyi Huang, Kaitlyn H Szalay, Abhishek Chatterjee.

Genetic code expansion (GCE) in mammalian cells has emerged as a powerful technology for investigating and engineering protein function. This method allows for the precise incorporation of a rapidly growing toolbox of noncanonical amino acids (ncAAs) into predefined sites of target proteins expressed in living cells. Due to the minimal size of these genetically encoded ncAAs, the wide range of functionalities they provide, and the ability to introduce them freely at virtually any site of any protein by simple mutagenesis, this technology holds immense potential for probing the complex biology of mammalian cells and engineering next-generation biotherapeutics. In this review, we provide an overview of the underlying machinery that enables ncAA mutagenesis in mammalian cells and how these are developed. We have also compiled an updated list of ncAAs that have been successfully incorporated into proteins in mammalian cells. Finally, we provide our perspectives on the current challenges that need to be addressed to fully harness the potential of this technology.

DOI: https://doi.org/10.1021/acs.chemrev.4c00730
Elife. 2025 Feb 12. pii: RP98110. [Epub ahead of print]13

A molecular proximity sensor based on an engineered, dual-component guide RNA.

Junhong Choi, Wei Chen, Hanna Liao, Xiaoyi Li, Jay Shendure.

  One of the goals of synthetic biology is to enable the design of arbitrary molecular circuits with programmable inputs and outputs. Such circuits bridge the properties of electronic and natural circuits, processing information in a predictable manner within living cells. Genome editing is a potentially powerful component of synthetic molecular circuits, whether for modulating the expression of a target gene or for stably recording information to genomic DNA. However, programming molecular events such as protein-protein interactions or induced proximity as triggers for genome editing remains challenging. Here, we demonstrate a strategy termed 'P3 editing', which links protein-protein proximity to the formation of a functional CRISPR-Cas9 dual-component guide RNA. By engineering the crRNA:tracrRNA interaction, we demonstrate that various known protein-protein interactions, as well as the chemically induced dimerization of protein domains, can be used to activate prime editing or base editing in human cells. Additionally, we explore how P3 editing can incorporate outputs from ADAR-based RNA sensors, potentially allowing specific RNAs to induce specific genome edits within a larger circuit. Our strategy enhances the controllability of CRISPR-based genome editing, facilitating its use in synthetic molecular circuits deployed in living cells.

Keywords:  CRISPR-Cas; genetics; genome editing; genomics; human; molecular recording; protein-protein interaction; synthetic biology

DOI:  https://doi.org/10.7554/eLife.98110
Protein Expr Purif. 2025 Feb 06. pii: S1046-5928(25)00025-7. [Epub ahead of print]229 106683

Production of recombinant coiled coil silk proteins for materials synthesis.

Patrick J Shilling, Luisa Pontes-Braz, Lachlan Mitchell, Linda Howell, Prem Veneer, Srinivasan Jayashree, Laura A Castelli, Tam Pham, Louis Lu, Bei Wang, K Y Benjamin Yeo, Surekha Nimma, Lyndall Briggs, Caitlin Johnston, Michelle Michie, Tara D Sutherland.

  Rational design of fundamentally new advanced materials would be facilitated by availability of polymers with controlled monomer sequence. Recombinant proteins offer polymers with controlled monomer sequence but are underrepresented in material science, in part because suitable proteins cannot be produced at commercial levels in recombinant systems. The silk proteins of honeybees fulfil the requirements for rational materials design and can be produced at commercially viable levels. In this study we compare recombinant expression of these silks in bacteria, yeast and insect cells to identify the most suitable method of silk protein production. Yeast and insect cell lines are unlikely to be suitable expression platforms for these silks as the recombinant proteins were degraded, expression levels were low or absent, and host cell protein levels were high. We confirm that expression into E. coli inclusion bodies using defined media offers high level expression and to date is the best expression system for these proteins.

Keywords:  Coiled coil; Escherichia coli; Insect cells; Recombinant production; Silk protein; Yeast

DOI:  https://doi.org/10.1016/j.pep.2025.106683
Nat Chem. 2025 Feb 10.

Synthetic biomolecular condensates enhance translation from a target mRNA in living cells.

Daniel Mark Shapiro, Sonal Deshpande, Seyed Ali Eghtesadi, Miranda Zhong, Cassio Mendes Fontes, David Fiflis, Dahlia Rohm, Junseon Min, Taranpreet Kaur, Joanna Peng, Max Ney, Jonathan Su, Yifan Dai, Aravind Asokan, Charles A Gersbach, Ashutosh Chilkoti.

Biomolecular condensates composed of proteins and RNA are one approach by which cells regulate post-transcriptional gene expression. Their formation typically involves the phase separation of intrinsically disordered proteins with a target mRNA, sequestering the mRNA into a liquid condensate. This sequestration regulates gene expression by modulating translation or facilitating RNA processing. Here we engineer synthetic condensates using a fusion of an RNA-binding protein, the human Pumilio2 homology domain (Pum2), and a synthetic intrinsically disordered protein, an elastin-like polypeptide (ELP), that can bind and sequester a target mRNA transcript. In protocells, sequestration of a target mRNA largely limits its translation. Conversely, in Escherichia coli, sequestration of the same target mRNA increases its translation. We characterize the Pum2-ELP condensate system using microscopy, biophysical and biochemical assays, and RNA sequencing. This approach enables the modulation of cell function via the formation of synthetic biomolecular condensates that regulate the expression of a target protein.

DOI: https://doi.org/10.1038/s41557-024-01706-7
RSC Adv. 2025 Feb 06. 15(6): 4693-4700

Chemical degradation as an enabling pathway to polymersome functionalization.

Chenyu Lin, Kumar Siddharth, Juan Pérez-Mercader.

Readiness and the ability to functionalize are the fundamental features of natural living systems. Understanding the chemical roots of functionalization is a basic quest for the generation of new materials in the laboratory and chemistry-based natural-life-mimicking artificial or synthetic living systems. Using polymerization-induced self-assembly (PISA) and starting from a homogeneous aqueous blend of a few strictly non-biochemical compounds, it is possible to create amphiphiles that can self-boot into submicron supramolecular objects (micelles). These micelles under the control of chemistry can undergo (1) morphological evolution into giant polymersomes and (2) exhibit growth-implosion cycles accompanied by (3) vesicle self-reproduction and population growth. We call the physico-chemical processes underlying these life-like systems "Phoenix dynamics". Herein, we studied how the emergence of such functions in these systems can occur owing to the combination of the chemical degradation of the macro chain transfer agents involved in the PISA process due to the presence of oxygen and its impact on the physico-chemical evolution of these objects. Results indicated implications for the controllable degradation-triggered functionalization of self-booted synthetic supramolecular self-assembling systems and provided a physicochemical pathway to implement novel functionalities in supramolecular systems. Functionalization of polymersomes is of interest in many areas of science and technology, including biomedical and environmental applications and origins of life studies.

DOI: https://doi.org/10.1039/d4ra08536a
Nat Commun. 2025 Feb 11. 16(1): 1551

Holographic tomographic volumetric additive manufacturing.

Maria Isabel Álvarez-Castaño, Andreas Gejl Madsen, Jorge Madrid-Wolff, Viola Sgarminato, Antoine Boniface, Jesper Glückstad, Christophe Moser.

Several 3D light-based printing technologies have been developed that rely on the photopolymerization of liquid resins. A recent method, so-called Tomographic Volumetric Additive Manufacturing, allows the fabrication of microscale objects within tens of seconds without the need for support structures. This method works by projecting intensity patterns, computed via a reverse tomography algorithm, into a photocurable resin from different angles to produce a desired 3D shape when the resin reaches the polymerization threshold. Printing using incoherent light patterning has been previously demonstrated. In this work, we show that a light engine with holographic phase modulation unlocks new potential for volumetric printing. The light projection efficiency is improved by at least a factor 20 over amplitude coding with diffraction-limited resolution and its flexibility allows precise light control across the entire printing volume. We show that computer-generated holograms implemented with tiled holograms and point-spread-function shaping mitigates the speckle noise which enables the fabrication of millimetric 3D objects exhibiting negative features of 31 μm in less than a minute with a 40 mW light source in acrylates and scattering materials, such as soft cell-laden hydrogels, with a concentration of 0.5 million cells per mL.

DOI: https://doi.org/10.1038/s41467-025-56852-4
Chem Sci. 2025 Feb 06.

Host-guest chemistry on living cells enabling recyclable photobiocatalytic cascade.

Jiaheng Zhang, Vasco F Batista, René Hübner, Henrik Karring, Changzhu Wu.

Combining chemical and whole-cell catalysts enables sustainable chemoenzymatic cascade reactions. However, their traditional combination faces challenges in catalyst recycling and maintaining cell viability. Here, we introduce a supramolecular host-guest strategy that efficiently attaches photocatalysts to bacterial cells, facilitating recyclable photobiocatalysis. This method involves attaching a cationic polyethylenimine (PEI) polymer, functionalized with β-cyclodextrin (β-CD), to E. coli cells. The polymer attachment is biocompatible and protective, safeguarding the cells from harsh conditions such as UV radiation and organic solvents, without causing cell death. Additionally, the presence of β-CD imparts a plug-and-play capability to the cells, enabling the straightforward integration of guest photocatalysts - specifically anthraquinone - onto the cell surface through host-guest interactions. This effective combination of cellular and chemical catalysts promotes efficient photobiocatalytic cascades and supports the photocatalyst's recycling and reuse. This supramolecular system thus represents a promising platform for advancing photobiocatalysis in cascade synthesis.

DOI: https://doi.org/10.1039/d4sc06508e
Proc Natl Acad Sci U S A. 2025 Feb 18. 122(7): e2409852122

Engineered immunological niche directs therapeutic development in models of progressive multiple sclerosis.

Laila M Rad, Kevin R Hughes, Sydney N Wheeler, Joseph T Decker, Sophia M Orbach, Angelica Galvan, Jasmine Thornhill, Kate V Griffin, Hamza Turkistani, Russell R Urie, David N Irani, Lonnie D Shea, Aaron H Morris.

  Primary progressive multiple sclerosis (MS) is a demyelinating autoimmune disease with only a single class of FDA-approved treatment, B cell depletion. Novel treatments could emerge from a deeper understanding of the interplay between multiple cell types within diseased tissue throughout progression. We initially describe an engineered biomaterial-based immunological niche (IN) as a surrogate for diseased tissue to investigate immune cell function and phenotype dynamics throughout a chronic progressive mouse model of MS. Using these niches, we identify an array of dysregulated CC chemokine signaling as potential targets. We then develop antigen-loaded nanoparticles that reduce CC chemokine signaling, while delivering antigen. These nanoparticles serve as an antigen-specific treatment, and a single injection reduces disease burden, even if administered after symptomatic disease onset. This report demonstrates proof of principle of a biomaterial scaffold as a diseased tissue surrogate that can monitor immune function, identify potential drug targets, and guide the development of a therapeutic.

Keywords:  autoimmunity; biomaterials; immunoengineering; multiple sclerosis; regenerative medicine

DOI:  https://doi.org/10.1073/pnas.2409852122
Biomater Sci. 2025 Feb 10.

Living material-derived intelligent micro/nanorobots.

Shuhuai Wang, Ya Liu, Shuangjiao Sun, Qinyi Gui, Wei Liu, Wei Long.

Living materials, which include various types of cells, organelles, and biological components from animals, plants, and microorganisms, have become central to recent investigations in micro and nanorobotics. Living material-derived intelligent micro/nanorobots (LMNRs) are self-propelled devices that combine living materials with synthetic materials. By harnessing energy from external physical fields or biological sources, LMNRs can move autonomously and perform various biomedical functions, such as drug delivery, crossing biological barriers, medical imaging, and disease treatment. This review, from a biomimetic strategy perspective, summarized the latest advances in the design and biomedical applications of LMNRs. It provided a comprehensive overview of the living materials used to construct LMNRs, including mammalian cells, plants, and microorganisms while highlighting their biological properties and functions. Lastly, the review discussed the major challenges in this field and offered suggestions for future research that may help facilitate the clinical application of LMNRs in the near future.

DOI: https://doi.org/10.1039/d4bm01685h
ACS Synth Biol. 2025 Feb 12.

De Novo Production of 1,6-Hexanediol and 1,6-Hexamethylenediamine from Glucose by Metabolic Engineered Escherichia coli.

Nan Qin, Fanghuan Zhu, Youmeng Liu, Dehua Liu, Zhen Chen.

  1,6-Hexamethylenediamine (HMD) and 1,6-hexanediol (HDO) are pivotal C6 platform chemicals with extensive applications as key monomers in the synthesis of nylons, polyurethanes, and polyesters. The biological production of HMD and HDO from cheap and renewable bioresources represents an environmentally benign strategy for the sustainable chemical industry. Herein, we report the development of a novel biocatalytic route for the direct conversion of d-glucose to HMD and HDO in Escherichia coli. This was achieved through the integration of an adipic acid synthesis module with conversion modules tailored for HMD and HDO production. The study entailed a comprehensive optimization of pathway enzymes, protein expression, and precursor supply. Furthermore, a co-culture fermentation strategy was employed to enhance the efficiency of labor division, resulting in a two-strain cocultivation process that yielded 16.62 mg/L of HMD and 214.93 mg/L of HDO using glucose as the sole carbon source. This study establishes a foundational framework for the advancement of sustainable biological production processes for HMD and HDO from renewable resources.

Keywords:  1,6-hexamethylenediamine; 1,6-hexanediol; Escherichia coli; adipic acid; co-culture; metabolic engineering

DOI:  https://doi.org/10.1021/acssynbio.4c00881
Chem Rev. 2025 Feb 10.

Optogenetics with Atomic Precision─A Comprehensive Review of Optical Control of Protein Function through Genetic Code Expansion.

Maura Charette, Carolyn Rosenblum, Olivia Shade, Alexander Deiters.

Conditional control of protein activity is important in order to elucidate the particular functions and interactions of proteins, their regulators, and their substrates, as well as their impact on the behavior of a cell or organism. Optical control provides a perhaps optimal means of introducing spatiotemporal control over protein function as it allows for tunable, rapid, and noninvasive activation of protein activity in its native environment. One method of introducing optical control over protein activity is through the introduction of photocaged and photoswitchable noncanonical amino acids (ncAAs) through genetic code expansion in cells and animals. Genetic incorporation of photoactive ncAAs at key residues in a protein provides a tool for optical activation, or sometimes deactivation, of protein activity. Importantly, the incorporation site can typically be rationally selected based on structural, mechanistic, or computational information. In this review, we comprehensively summarize the applications of photocaged lysine, tyrosine, cysteine, serine, histidine, glutamate, and aspartate derivatives, as well as photoswitchable phenylalanine analogues. The extensive and diverse list of proteins that have been placed under optical control demonstrates the broad applicability of this methodology.

DOI: https://doi.org/10.1021/acs.chemrev.4c00224
Adv Mater. 2025 Feb 09. e2419906

Biopolymeric Gels: Advancements in Sustainable Multifunctional Materials.

Chuxin Lei, Qing Li, Wenshuai Chen, Guihua Yu.

  With the growing emphasis on building a global sustainable community, biopolymeric gels have emerged as a promising platform for environmentally friendly and sustainable applications, garnering significant research attention. Compared to conventional synthetic gels, biopolymeric gels offer numerous advantages, including abundant and renewable raw materials, energy-efficient and eco-friendly fabrication processes, tunable physicochemical properties, and superior biocompatibility and biodegradability. This review provides a comprehensive overview of recent advancements in multifunctional biopolymeric gels. It begins by introducing various biopolymeric building blocks and their intrinsic properties across multiple scales. Subsequently, the synthetic strategies for biopolymeric gels are thoroughly discussed, emphasizing versatile gelation strategies, multiple approaches for fabricating gels, diverse processing approaches to achieve tailorable gels with desired functionalities. The sustainable applications of biopolymeric gels are systematically explored, focusing on their roles in energy storage, environmental remediation of water management, thermal management, and bioelectronics. Finally, the review concludes with an outlook on the challenges and opportunities for advancing biopolymeric gels as key materials in the pursuit of sustainability.

Keywords:  aerogels; biopolymers; functional materials; hydrogels; sustainable

DOI:  https://doi.org/10.1002/adma.202419906
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2025 Jan-Feb;17(1):17(1): e70003

Spontaneous Self-Organized Order Emerging From Intrinsically Disordered Protein Polymers.

Sergio Acosta, Pablo Rodríguez-Alonso, Viktoriya Chaskovska, Julio Fernández-Fernández, José Carlos Rodríguez-Cabello.

  Intrinsically disordered proteins (IDPs) are proteins that, despite lacking a defined 3D structure, are capable of adopting dynamic conformations. This structural adaptability allows them to play not only essential roles in crucial cellular processes, such as subcellular organization or transcriptional control, but also in coordinating the assembly of macromolecules during different stages of development. Thus, in order to artificially replicate the complex processes of morphogenesis and their dynamics, it is crucial to have materials that recapitulate the structural plasticity of IDPs. In this regard, intrinsically disordered protein polymers (IDPPs) emerge as promising materials for engineering synthetic condensates and creating hierarchically self-assembled materials. IDPPs exhibit remarkable properties for their use in biofabrication, such as functional versatility, tunable sequence order-disorder, and the ability to undergo liquid-liquid phase separation (LLPS). Recent research has focused on harnessing the intrinsic disorder of IDPPs to design complex protein architectures with tailored properties. Taking advantage of their stimuli-responsiveness and degree of disorder, researchers have developed innovative strategies to control the self-assembly of IDPPs, resulting in the creation of hierarchically organized structures and intricate morphologies. In this review, we aim to provide an overview of the latest advances in the design and application of IDPP-based materials, shedding light on the fundamental principles that control their supramolecular assembly, and discussing their application in the biomedical and nanobiotechnological fields.

Keywords:  complex morphogenesis; elastin‐like recombinamers; intrinsically disordered proteins; liquid–liquid phase separation; resilin‐like recombinamers

DOI:  https://doi.org/10.1002/wnan.70003
Annu Rev Biophys. 2025 Feb 10.

Information Processing in Biochemical Networks.

Gašper Tkačik, Pieter Rein Ten Wolde.

Living systems are characterized by controlled flows of matter, energy, and information. While the biophysics community has productively engaged with the first two, addressing information flows has been more challenging, with some scattered success in evolutionary theory and a more coherent track record in neuroscience. Nevertheless, interdisciplinary work of the past two decades at the interface of biophysics, quantitative biology, and engineering has led to an emerging mathematical language for describing information flows at the molecular scale. This is where the central processes of life unfold: from detection and transduction of environmental signals to the readout or copying of genetic information and the triggering of adaptive cellular responses. Such processes are coordinated by complex biochemical reaction networks that operate at room temperature, are out of equilibrium, and use low copy numbers of diverse molecular species with limited interaction specificity. Here we review how flows of information through biochemical networks can be formalized using information-theoretic quantities, quantified from data, and computed within various modeling frameworks. Optimization of information flows is presented as a candidate design principle that navigates the relevant time, energy, crosstalk, and metabolic constraints to predict reliable cellular signaling and gene regulation architectures built of individually noisy components.

DOI: https://doi.org/10.1146/annurev-biophys-060524-102720
J Biol Eng. 2025 Feb 10. 19(1): 14

Modular plasmid design for autonomous multi-protein expression in Escherichia coli.

Agata Matera, Kinga Dulak, Sandra Sordon, Ewa Huszcza, Jarosław Popłoński.

   BACKGROUND: Molecular and synthetic biology tools enable the design of new-to-nature biological systems, including genetically engineered microorganisms, recombinant proteins, and novel metabolic pathways. These tools simplify the development of more efficient, manageable, and tailored solutions for specific applications, biocatalysts, or biosensors that are devoid of undesirable characteristics. The key aspect of preparing these biological systems is the availability of appropriate strategies for designing novel genetic circuits. However, there remains a pressing need to explore independent and controllable systems for the co-expression of multiple genes.
RESULTS: In this study, we present the characterisation of a set of bacterial plasmids dedicated to recombinant expression in broadly used Escherichia coli. The set includes plasmids with four different, most commonly used bacterial expression cassettes - RhaS/RhaBAD, LacI/Trc, AraC/AraBAD, and XylS/Pm, which can be used alone or freely combined in up to three-gene monocistronic expression systems using Golden Standard Molecular Cloning kit assembly. The independent induction of each of the designed cassettes enables the autonomous expression of up to three recombinant proteins from one plasmid. The expression of a triple-enzyme cascade consisting of sucrose synthase, UDP-rhamnose synthase and flavonol-7-O-rhamnosyltransferase, confirmed that the designed system can be applied for the complex biocatalysts production.
CONCLUSIONS: Presented herein strategy for the multigene expression is a valuable addition to the current landscape of different co-expression approaches. The thorough characterisation of each expression cassette indicated their strengths and potential limitations, which will be useful for subsequent investigations in the field. The defined cross-talks brought a better understanding of the metabolic mechanisms that may affect the heterologous expression in the bacterial hosts.

Keywords:  Expression system; Heterologous expression; Inducible promoter; Rhamnosylation; Synthetic plasmid; Transcriptional factor

DOI:  https://doi.org/10.1186/s13036-025-00483-2
Proc Natl Acad Sci U S A. 2025 Feb 18. 122(7): e2416536122

Geometric modeling of knitted fabrics.

Lauren Niu, Geneviève Dion, Randall D Kamien.

  Knitting can turn a one-dimensional yarn into a highly ramified three-dimensional structure. As a method of additive manufacturing, it holds promise for a class of lightweight, ultrastrong materials. Here, we present a purely geometric model to predict the three-dimensional self-folding of knitted fabrics made only of the two traditional stitches, knit and purl.

Keywords:  geometry; knitting; origami; textile

DOI:  https://doi.org/10.1073/pnas.2416536122
Mater Today Bio. 2025 Apr;31 101509

DNA-encoded dynamic hydrogels for 3D bioprinted cartilage organoids.

Ziyu Chen, Hao Zhang, Jingtao Huang, Weizong Weng, Zhen Geng, Mengmeng Li, Jiacan Su.

  Articular cartilage, composed of chondrocytes within a dynamic viscoelastic matrix, has limited self-repair capacity, posing a significant challenge for regeneration. Constructing high-fidelity cartilage organoids through three-dimensional (3D) bioprinting to replicate the structure and physiological functions of cartilage is crucial for regenerative medicine, drug screening, and disease modeling. However, commonly used matrix bioinks lack reversible cross-linking and precise controllability, hindering dynamic cellular regulation. Thus, encoding bioinks adaptive for cultivating cartilage organoids is an attractive idea. DNA, with its ability to be intricately encoded and reversibly cross-linked into hydrogels, offers precise manipulation at both molecular and spatial structural levels. This endows the hydrogels with viscoelasticity, printability, cell recognition, and stimuli responsiveness. This paper elaborates on strategies to encode bioink via DNA, emphasizing the regulation of predictable dynamic properties and the resulting interactions with cell behavior. The significance of these interactions for the construction of cartilage organoids is highlighted. Finally, we discuss the challenges and future prospects of using DNA-encoded hydrogels for 3D bioprinted cartilage organoids, underscoring their potential impact on advancing biomedical applications.

Keywords:  Bioprinting; Cartilage organoids; DNA hydrogel; Tissue engineering

DOI:  https://doi.org/10.1016/j.mtbio.2025.101509
Proc Natl Acad Sci U S A. 2025 Feb 18. 122(7): e2417065122

Spatial population dynamics of bacterial colonies with social antibiotic resistance.

Marlis K Denk-Lobnig, Kevin B Wood.

  Bacteria frequently inhabit surface-attached communities where rich "social" interactions can significantly alter their population-level behavior, including their response to antibiotics. Understanding these collective effects in spatially heterogeneous communities is an ongoing challenge. Here, we investigated the spatial organization that emerges from antibiotic exposure in initially randomly distributed communities containing antibiotic-resistant and -sensitive strains of Enterococcus faecalis, an opportunistic pathogen. We identified that a range of complex spatial structures emerged in the population homeland-the inoculated region that microbes inhabit prior to range expansion-which depended on initial colony composition and antibiotic concentration. We found that these arrangements were explained by cooperative interactions between resistant and sensitive subpopulations with a variable spatial scale, the result of dynamic zones of protection afforded to sensitive cells by growing populations of enzyme-producing resistant neighbors. Using a combination of experiments and mathematical models, we explored the complex spatiotemporal interaction dynamics that create these patterns, and predicted spatial arrangements of sensitive and resistant subpopulations under new conditions. We illustrated how spatial population dynamics in the homeland affect subsequent range expansion, both because they modulate the composition of the initial expanding front, and through long-range cooperation between the homeland and the expanding region. Finally, we showed that these spatial constraints resulted in populations whose size and composition differed markedly from matched populations in well-stirred (planktonic) cultures. These findings underscore the importance of spatial structure and cooperation, long-studied features in theoretical ecology, for determining the fate of bacterial communities under antibiotic exposure.

Keywords:  antibiotic; biofilm; pattern formation

DOI:  https://doi.org/10.1073/pnas.2417065122
Biochemistry. 2025 Feb 11.

Distinct Acyl Carrier Protein Docking Sites Help Mediate the Opposite Stereoselectivities of A- and B-type Modular Polyketide Synthase Ketoreductases.

Katherine A Ray, Sally N Lin, Adrian T Keatinge-Clay.

The domains of modular polyketide synthases (PKSs) collaborate to extend and process polyketide intermediates; however, most of their interactions with one another remain mysterious. We used AlphaFold 2 to investigate how acyl carrier proteins (ACPs) present intermediates to ketoreductases (KRs), processing domains capable of not only setting the stereochemical orientations of β-hydroxyl substituents but also of α-substituents. In modules that do not contain a dehydratase (DH), the A- and B-type KRs that, respectively, generate l- and d-oriented β-hydroxy groups are predicted to possess distinct ACP docking sites. In modules containing DHs, where A-type KRs are much less common, both KR types are predicted to possess an ACP-docking site equivalent to that of B-type KRs from modules without DHs. To investigate this most common ACP docking site, mutagenesis was performed on 20 residues of the KR from the second pikromycin module within the model triketide synthase P1-P2-P7. The least active variants are those with mutations to a conserved hydrophobe, 2 residues downstream of the LDD motif of B-type KRs, predicted to insert into a hole adjacent to the phosphopantetheinylated serine of ACP.

DOI: https://doi.org/10.1021/acs.biochem.4c00565
bioRxiv. 2025 Jan 10. pii: 2025.01.10.632339. [Epub ahead of print]

Dynamic global acetylation remodeling during the yeast heat shock response.

Rebecca E Hardman-Kavanaugh, Aaron J Storey, Tara N Stuecker, Stephanie E Hood, Gregory A Barrett-Wilt, Venkata R Krishnamurthi, Yong Wang, Stephanie D Byrum, Samuel G Mackintosh, Rick D Edmondson, Wayne P Wahls, Alan J Tackett, Jeffrey A Lewis.

All organisms experience stress and must rapidly respond to changing conditions. Thus, cells have evolved sophisticated rapid-response mechanisms such as post-translational protein modification to rapidly and reversibly modulate protein activity. One such post-translational modification is reversible lysine acetylation, where proteomic studies have identified thousands of acetylated proteins across diverse organisms. While the sheer size of the 'acetylome' is striking, the function of acetylation for the vast majority of proteins remains largely obscure. Here, we show that global acetylation plays a previously unappreciated role in the heat shock response of Saccharomyces cerevisiae. We find that dysregulated acetylation renders cells heat sensitive, and moreover, that the acetylome is globally remodeled during heat shock over time. Using quantitative acetyl-proteomics, we identified ∼400 high-confidence acetyl marks across ∼200 proteins that significantly change in acetylation when cells are shifted to elevated temperature. Proteins with significant changes in lysine acetylation during heat shock strongly overlap with genes induced or repressed by stress. Thus, we hypothesize that protein acetylation augments the heat shock response by activating induced proteins and inactivating repressed proteins. Intriguingly, we find nearly 40 proteins with at least two acetyl marks that significantly change in the opposite directions. These proteins are strongly enriched for chaperones and ribosomal proteins, suggesting that these two key processes are coordinately regulated by protein acetylation during heat shock. Moreover, we hypothesize that the same type of activating and inactivating marks that exist on histones may be a general feature of proteins regulated by acetylation. Overall, this work has identified a new layer of post-translational regulation that likely augments the classic heat shock response.

DOI: https://doi.org/10.1101/2025.01.10.632339
Adv Colloid Interface Sci. 2025 Feb 03. pii: S0001-8686(25)00031-4. [Epub ahead of print]339 103420

Localized assembly in biological activity: Origin of life and future of nanoarchitectonics.

Jingwen Song, Kohsaku Kawakami, Katsuhiko Ariga.

  The concept of nanoarchitectonics has emerged as a post-nanotechnology paradigm in the field of functional materials development. This concept entails the construction of functional material systems at the nanoscale, based on the knowledge acquired from nanotechnology. In biological systems, advanced nanoarchitectonics is achieved through precise structural organization governed by spatial localization, a process facilitated by localized assembly mechanisms. A thorough understanding of the principles of localized assembly is crucial for the creation of complex, asymmetric, hierarchical organizations that are similar in structure and function to living organisms. This review explores the concept of localized assembly, highlighting its biological inspiration, providing representative examples, and discussing its contributions to nanoarchitectonics. Key examples include assemblies using biological materials, those mimicking cellular functions, and those occurring within cells. Additionally, the role of interfacial interactions and liquid-liquid phase separation in localized assembly is emphasized. Particularly, the utilization of liquid-liquid phase separation demonstrates a remarkable capacity for forming intricate compartmentalized structures without discernible membranes, paving the way for multifunctional, localized systems. These localized assemblies are fundamental to essential biological functions and provide valuable insights into the molecular mechanisms underlying the origin of cells and life. Such understanding holds significant promise for advancing materials nanoarchitectonics, particularly in biomedical applications.

Keywords:  All water system; Interface; Liquid-liquid phase separation; Localized assembly; Membraneless organelle; Nanoarchitectonics; Origin of life

DOI:  https://doi.org/10.1016/j.cis.2025.103420
Small. 2025 Feb;21(6): e2408822

High-Resolution Self-Assembly of Functional Materials and Microscale Devices via Selective Plasma Induced Surface Energy Programming.

Luke J Tinsley, Prakash Karipoth, James H Chandler, Silvia Taccola, Pietro Valdastri, Russell A Harris.

  Current technologies preclude effective and efficient self-assembly of heterogeneous arrangements of functional materials between 10-1 and 10-5 m. Consequently, their fabrication is dominated by methods of direct material manipulation, which struggle to meet the designers' demands regarding resolution, material freedom, production time, and cost. A two-step, computer-controlled is presented, multi-material self-assembly technique that allows heterogenous patterns of several centimeters with features down to 12.5 µm in size. First, a micro plasma jet selectively programs the surface energy of a polydimethylsiloxane substrate through localized chemical functionalization. Second, polar fluids containing functional materials are simplistically introduced which then self-assemble according to the patterned regions of high surface energy over timescales of the order of seconds. In-process control enables both high-resolution patterning and high throughput. This approach is demonstrated to produce heterogenous patterns of materials with varying conductive, magnetic, and mechanical properties. These include magneto-mechanical films and flexible electronic devices with unprecedented processing times and economy for high-resolution patterns. This self-assembly approach can disrupt the current lithography/direct write paradigm that dominates micro/meso-fabrication, enabling the next generation of devices across a broad range of fields via a flexible, industrially scalable, and environmentally friendly manufacturing route.

Keywords:  Atmospheric Plasma; Flexible Electronics; Functional Materials; Microfabrication; Soft Robotics; current keywords: Self‐assembly

DOI:  https://doi.org/10.1002/smll.202408822
Metab Eng. 2025 Feb 11. pii: S1096-7176(25)00010-2. [Epub ahead of print]

Metabolic division engineering of Escherichia coli consortia for de novo biosynthesis of flavonoids and flavonoid glycosides.

Zetian Qiu, Yumei Han, Jia Li, Yi Ren, Xue Liu, Shengying Li, Guang-Rong Zhao, Lei Du.

  Heterologous biosynthesis of natural products with long biosynthetic pathways in microorganisms often suffers from diverse problems, such as enzyme promiscuity and metabolic burden. Flavonoids and their glycosides are important phytochemicals in the diet of human beings, with various health benefits and biological activities. Despite previous efforts and achievements, efficient microbial production of plant-derived flavonoid compounds with long pathways remains challenging. Herein, we applied metabolic division engineering of Escherichia coli consortia to overcome these limitations. By establishing new biosynthetic pathways, rationally adjusting metabolic node intermediates, and engineering different auxotrophic and orthogonal carbon sources for hosts, we established stable two- and three-bacteria co-culture systems to efficiently de novo produce 12 flavonoids (61.15-325.31 mg/L) and 36 corresponding flavonoid glycosides (1.31-191.79 mg/L). Furthermore, the co-culture system was rapidly extended in a plug-and-play manner to produce isoflavonoids, dihydrochalcones, and their glycosides. This study successfully alleviates metabolic burden and overcomes enzyme promiscuity, and provides significant insights that could guide the biosynthesis of other complex secondary metabolites.

Keywords:  coculture; flavonoid glycosides; flavonoids; metabolic division engineering; metabolic engineering; synthetic biology

DOI:  https://doi.org/10.1016/j.ymben.2025.02.001
Chembiochem. 2025 Feb 11. e202401040

Boronic Acid-Linked Apo-Zinc Finger Protein for Ubiquitin Delivery in Live Cells.

Pritam Ghosh, Oliver Seitz.

  Delivering cargo into living cells has extensive applications in chemistry, biology, and medicine. Cell-penetrating peptides (CPPs) provide an ideal solution for cellular delivery. Enhancing CPPs with additional functional units can improve delivery efficiency. We investigate the conjugation of boronic acid modules to enhance internalization through interactions with cell surface glycans. The aim of this study is to determine whether adding boronic acid can transform a peptide that typically lacks CPP properties into one that functions as a CPP, enabling the delivery of crucial biological cargo like ubiquitin. The zinc finger protein in its apo state was selected as a "boronate-enabled" CPP. Results indicate that skeletal point mutations and post-synthetic modifications, combined with conjugated benzoboroxole derivatives, enable the apo-ZFP the ability to transport ubiquitin within A549 cells, confirmed through microscopy and flow cytometry. This effective internalization of cargo offers valuable insights for advancing the development of boronic acid-mediated cell-penetrating peptides.

Keywords:  Boronic Acid * Ubiquitin * Live Cells * Cell Penetrating Peptide *

DOI:  https://doi.org/10.1002/cbic.202401040
ACS Nano. 2025 Feb 12.

Controllable Polymerization of Inorganic Ionic Oligomers for Precise Nanostructural Construction in Materials.

Yan He, Weifeng Fang, Ruikang Tang, Zhaoming Liu.

  The rational design of nanostructures is critical for achieving high-performance materials. The close-packing behavior of inorganic ions and their less controllable nucleation process impede the precise nanostructural construction of inorganic ionic compounds. The discovery of inorganic ionic oligomers (stable molecular-scale inorganic ionic compounds) and their polymerization reaction enables the controllable arrangement of inorganic ions for diverse nanostructures. This perspective aims to introduce inorganic ionic oligomers and their currently identified advantages in the precise design of inorganic and organic-inorganic hybrid nanostructures, directing the development of advanced materials with applications across the mechanical, energy, environmental, and biomedical fields. The challenges and opportunities for the controllable polymerization of inorganic ionic oligomers are presented at the end of this perspective. We suggest that inorganic ionic oligomers and their polymerization reaction offer a promising strategy for the preparation of inorganic and organic-inorganic hybrid materials.

Keywords:  inorganic ionic compound; inorganic ionic oligomers; inorganic ionic polymerization reaction; materials chemistry; nanostructure

DOI:  https://doi.org/10.1021/acsnano.4c18704
Nat Commun. 2025 Feb 12. 16(1): 1556

Fully addressable designer superstructures assembled from one single modular DNA origami.

Johann M Weck, Amelie Heuer-Jungemann.

DNA nanotechnology and especially the DNA origami method are primal tools to create precise nanoscale objects. For DNA origami, a long ssDNA scaffold strand is folded by a multitude of smaller staple strands into base-pair accurate shapes, allowing for precise modification and incorporation of guest molecules. However, DNA origami are limited in size, and thus is the area that can be controlled with nanoscale precision. Prior methods of creating larger assemblies were either costly or lacked structural control. Here, we incorporate two methods of modularity into one exemplary modular DNA origami (moDON). The modularity allows for the creation of over 50,000 diverse monomers and subsequently the assembly of a plethora of fully addressable designer superstructures while keeping the construction cost very low. The here-introduced methods for modularity in DNA origami design offer an efficient, cost-effective solution for constructing precisely organized, and fully addressable structures on a variety of scales.

DOI: https://doi.org/10.1038/s41467-025-56846-2
Adv Mater. 2025 Feb 11. e2408616

Dynamic and Reversible Tuning of Hydrogel Viscoelasticity by Transient Polymer Interactions for Controlling Cell Adhesion.

Shane Scott, Maria Villiou, Federico Colombo, Angeles De la Cruz-García, Leon Tydecks, Lotta Toelke, Katharina Siemsen, Christine Selhuber-Unkel.

  Cells are highly responsive to changes in their mechanical environment, influencing processes such as stem cell differentiation and tumor progression. To meet the growing demand for materials used for high throughput mechanotransduction studies, simple means of dynamically adjusting the environmental viscoelasticity of cell cultures are needed. Here, a novel method is presented to dynamically and reversibly control the viscoelasticity of naturally derived polymer hydrogels through interactions with poly (ethylene glycol) (PEG). Interactions between PEG and hydrogel polymers, possibly involving hydrogen bonding, stiffen the hydrogel matrices. By dynamically changing the PEG concentration of the solution in which polymer hydrogels are incubated, their viscoelastic properties are adjusted, which in turn affects cell adhesion and cytoskeletal organization. Importantly, this effects is reversible, providing a cost-effective and simple strategy for dynamically adjusting the viscoelasticity of polymer hydrogels. This method holds promise for applications in mechanobiology, biomedicine, and the life sciences.

Keywords:  controlled cell culture; dynamic cell culture; hydrogels; hydrogen bonding; reversible viscoelastic properties

DOI:  https://doi.org/10.1002/adma.202408616
Adv Mater. 2025 Feb 09. e2414703

Functional Biomaterials Derived from Protein Liquid-Liquid Phase Separation and Liquid-to-Solid Transition.

Tianchen Li, Dea Ilhamsyah, Benedict Tai, Yi Shen.

  Protein phase transitions play a vital role in both cellular functions and pathogenesis. Dispersed proteins can undergo liquid-liquid phase separation to form condensates, a process that is reversible and highly regulated within cells. The formation and physicochemical properties of these condensates, such as composition, viscosity, and multiphase miscibility, are precisely modulated to fulfill specific biological functions. However, protein condensates can undergo a further liquid-to-solid state, forming β-sheet-rich aggregates that may disrupt cellular function and lead to diseases. While this phenomenon is crucial for biological processes and has significant implications for neurodegenerative diseases, the phase behavior of naturally derived or engineered proteins and polypeptides also presents opportunities for developing high-performance, multifunctional materials at various scales. Additionally, the unique molecular recruitment capabilities of condensates inspire innovative advancements in biomaterial design for applications in drug discovery, delivery, and biosynthesis. This work highlights recent progress in understanding the mechanisms underlying protein phase behavior, particularly how it responds to internal molecular changes and external physical stimuli. Furthermore, the fabrication of multifunctional materials derived from diverse protein sources through controlled phase transitions is demonstrated.

Keywords:  liquid‐to‐solid transition; liquid–liquid phase separation; protein condensate; protein self‐assembly

DOI:  https://doi.org/10.1002/adma.202414703
Nat Commun. 2025 Feb 13. 16(1): 1400

Bacteria encode post-mortem protein catabolism that enables altruistic nutrient recycling.

Savannah E R Gibson, Isabella Frost, Stephen J Hierons, Tessa Moses, Wilson C K Poon, Stuart A West, Martin J Cann.

Bacterial death is critical in nutrient recycling. However, the underlying mechanisms that permit macromolecule recycling after bacterial death are largely unknown. We demonstrate that bacteria encode post-mortem protein catabolism via Lon protease released from the dead bacteria. Growth assays reveal that the lysate of Lon protease-null bacteria does not provide a growth benefit to wild type cells. This deficiency is reversed with exogenous recombinant Lon protease, confirming its post-mortem role and is independent of Lon ATPase activity. Biochemistry, growth assays and metabolomics demonstrate that Lon protease facilitates peptide nutrient release, benefitting living cells and acting as a cooperative public good. We also show that the production of Lon protease cannot be explained by a personal benefit to living cells. Although Lon protease can also provide a benefit to living cells under stressful conditions by helping control protein quality, this private benefit does not outweigh the cost under the conditions examined. These results suggest that Lon protease represents a post-mortem adaptation that can potentially be explained by considering the post-mortem indirect benefit to other cells (kin selection). This discovery highlights an unexpected post-mortem biochemistry, reshaping our understanding of nutrient recycling.

DOI: https://doi.org/10.1038/s41467-025-56761-6
Nature. 2025 Feb 12.

A bacterial antiviral system detects and directly fights against infection.



Keywords:  Immunology; Microbiology; Structural biology

DOI:  https://doi.org/10.1038/d41586-025-00416-5
ACS Synth Biol. 2025 Feb 10.

Tumor-Targeted Delivery of PD-1-Displaying Bacteriophages by Escherichia coli for Adjuvant Treatment of Colorectal Cancer.

Hong-Rui Li, Ying Zhou, Bang-Ce Ye.

  Bacteriophages, leveraging phage display and chemical modification, have the potential to deliver large payloads of antitumor agents with precision and to advance vaccine development. However, systemic phage administration often induces neutralizing antibodies, which accelerate phage clearance and reduce accumulation at the target site. To address this limitation, we propose a genetically modified nonpathogenic bacterial strain that specifically targets tumors and releases programmed death ligand 1 (PD-L1)-specific M13 bacteriophage within tumor tissue. We assessed the antitumor efficacy of this phage-expressing strain as an adjunctive therapeutic strategy along with a therapeutic bacterial strain engineered for the controlled release of an immunotoxin. The combination of these strains demonstrated synergistic effects in eliciting antitumor immune responses and inhibiting tumor growth in a murine model of colorectal cancer (CRC). Moreover, when combined with Folfox, the phage-expressing strain significantly extended the survival. This strategy of in vivo expression and tumor-specific release mediated by nonpathogenic bacterial strains provides an effective and safe method for targeted therapeutic phage delivery to tumors.

Keywords:  bacterial therapy; colorectal cancer; engineered bacteria; filamentous phage; immunotoxin

DOI:  https://doi.org/10.1021/acssynbio.4c00570
Adv Mater. 2025 Feb 13. e2420319

Molecularly Functionalized Biomass Hydrogels for Sustainable Atmospheric Water Harvesting.

Weixin Guan, Yaxuan Zhao, Chuxin Lei, Yuyang Wang, Kai Wu, Guihua Yu.

  Atmospheric water harvesting (AWH) offers a promising pathway to alleviate global water scarcity, highlighting the need for environmentally responsible sorbent materials. In this context, this research introduces a universal strategy for transforming natural polysaccharides into effective hydrogel sorbents, demonstrated with cellulose, starch, and chitosan. The methodology unites alkylation to graft thermoresponsive groups, thereby enhancing water processability and enabling energy-efficient water release at lower temperatures, with the integration of zwitterionic groups to ensure stable and effective water sorption. The molecularly functionalized cellulose hydrogel, exemplifying our approach, shows favorable water uptake of 0.86-1.32 g g-1 at 15-30% relative humidity (RH), along with efficient desorption, releasing 95% of captured water at 60 °C. Outdoor tests highlight the water production rate of up to 14.19 kg kg-1 day-1 by electrical heating. The proposed molecular engineering methodology, which expands the range of raw materials by leveraging abundant biomass feedstock, has the potential to advance sorbent production and scalable AWH technologies, contributing to sustainable solutions.

Keywords:  atmospheric water harvesting; biomass; cellulose; chitosan; hydrogels; molecular engineering; starch

DOI:  https://doi.org/10.1002/adma.202420319
Heliyon. 2025 Feb 15. 11(3): e41985

Hybrid mechanical metamaterials: Advances of multi-functional mechanical metamaterials with simultaneous static and dynamic properties.

Ana Carolina Azevedo Vasconcelos, Dingena Schott, Jovana Jovanova.

  Mechanical metamaterials are architected structures with unique functionalities, such as negative Poisson's ratio and negative stiffness, which are widely employed for absorbing energy of quasi-static and impact loads, giving improved mechanical response. Acoustic/elastic metamaterials, their dynamic counterparts, rely on frequency-dependent properties of their microstructure elements, including mass density and bulk modulus, to control the propagation of waves. Although such metamaterials introduced significant contribution for solving independently static and dynamic problems, they were facing certain resistance to their use in real-world engineering problems, mainly because of a lack of integrated systems possessing both mechanical and vibration attenuation performance. Advances in manufacturing processes and material and computational science now enable the creation of hybrid mechanical metamaterials, offering multifunctionality in terms of simultaneous static and dynamic properties, giving them the ability of controlling waves while withstanding the applied loading conditions. Exploring towards this direction, this review paper introduces the hybrid mechanical metamaterials in terms of their design process and multifunctional properties. We emphasize the still remaining challenges and how they can be potentially implemented as engineering solutions.

Keywords:  Energy absorption; Engineering problems; Hybrid mechanical metamaterials; Multi-functionality; Vibration attenuation

DOI:  https://doi.org/10.1016/j.heliyon.2025.e41985
Proc Natl Acad Sci U S A. 2025 Feb 18. 122(7): e2417075122

Turbulent mixing controls fixation of growing antagonistic populations.

Jonathan Bauermann, Roberto Benzi, David R Nelson, Suraj Shankar, Federico Toschi.

  Unlike coffee and cream that homogenize when stirred, growing micro-organisms (e.g., bacteria, baker's yeast) can actively kill each other and avoid mixing. How do such antagonistic interactions impact the growth and survival of competing strains, while being spatially advected by turbulent flows? By using numerical simulations of a continuum model, we study the dynamics of two antagonistic strains that are dispersed by incompressible turbulent flows in two spatial dimensions. A key parameter is the ratio of the fluid transport time to that of biological reproduction, which determines the winning organism that ultimately takes over the whole population from an initial heterogeneous state, a process known as fixation. By quantifying the probability and mean time for fixation along with the spatial structure of concentration fluctuations, we demonstrate how turbulence raises the threshold for biological nucleation and antagonism suppresses flow-induced mixing by depleting the population at interfaces. Our work highlights the unusual biological consequences of the interplay of turbulent fluid flows with antagonistic population dynamics, with potential implications for marine microbial ecology and origins of biological chirality.

Keywords:  antagonism; nonreciprocal interactions; spatial population dynamics; turbulent mixing

DOI:  https://doi.org/10.1073/pnas.2417075122
Mater Today Bio. 2025 Apr;31 101510

Injectable hyaluronic acid-based hydrogel niches to create localized and time-controlled therapy delivery.

Veronica Torresan, Alessandro Gandin, Paolo Contessotto, Francesca Zanconato, Giovanna Brusatin.

  The use of hydrogel-based niches for therapy delivery enables the concentration of active components and cells in a targeted area. This approach enhances efficacy while minimizing systemic side effects by spatially controlling the release of the therapy. Precise tuning of the matrix's chemical properties and control of both material degradation and release profile of biologically active components are required to reduce the optimal dose and extend its therapeutic effect. Here we aimed to develop an injectable hydrogel that can fulfill all these requirements. We designed a system based on hyaluronic acid, crosslinked via click-reaction with multi-arm polyethyleneglycol and functionalized with RGD peptides. Additionally, we incorporated thiol-modified heparin into the formulation, which provides specific binding sites for cytokines. Our results indicate that heparin incorporation can delay cytokine release, while the release of nanocarriers can be regulated by adjusting the crosslinking degree. This design modulates pore size and degradation time, while preserving the injectability of the niche. In conclusion, this system offers a versatile and efficient delivery platform suitable for therapeutic applications in a wide range of diseases.

Keywords:  Hydrogel niches; Injectable hydrogels; Therapies delivery

DOI:  https://doi.org/10.1016/j.mtbio.2025.101510
ACS Appl Bio Mater. 2025 Feb 13.

Polyacrylamide-Based Hydrogel with Biocompatibility and Tunable Stiffness for Three-Dimensional Cell Culture.

Yi Wang, Rui Zhang, Ziwen Qiao, Bohan Dou, Hongwei Xu, Fanlu Meng, Jianyong Huang.

  Three-dimensional (3D) culture of cells has gained increasing popularity because of its enhanced physiological relevance and more accurate representation of in vivo tissues. Matrigel, alginate, hyaluronic acid, and collagen are biocompatible 3D culture platforms with cell biofunctions, while it is difficult to decouple the biofunctions with mechanical properties. Polyacrylamide (PAAm) is a biocompatible but biologically nonfunctional platform heavily used in 2D culture. However, the cytotoxicity of acrylamide (AAm) prevents the application of PAAm as a platform for the 3D culture. Here, through RAFT copolymerization of AAm with a primary amine-bearing functional monomer, followed by postpolymerization modification, we synthesized nontoxic, linear PAAm featuring either multithiol or multinorbornene groups, available in various chain lengths. PAAm networks were fabricated by photoinduced thiol-norbornene coupling. The resulting PAAm hydrogel was biocompatible and structurally homogeneous with highly tunable and reproducible mechanical properties. PAAm hydrogels supported the 3D culture of human umbilical vein endothelial cells (HUVECs), where a higher adhesive ligand density promoted the viability of HUVECs. Furthermore, in combination with Matrigel, the PAAm hydrogel was used in the 3D culture of intestinal organoids, demonstrating that a lower mechanical strength was favorable. In summary, this report paves the way for the use of PAAm hydrogels in 3D culture, which is especially appealing for the decoupling of biological functions and mechanical properties.

Keywords:  3D cell culture; Polyacrylamide; RAFT polymerization; hydrogel; thiol-norbornene coupling

DOI:  https://doi.org/10.1021/acsabm.4c01846
Science. 2025 Jan 02. 387(6735): eado5068

Conformational ensembles reveal the origins of serine protease catalysis.

Siyuan Du, Rachael C Kretsch, Jacob Parres-Gold, Elisa Pieri, Vinícius Wilian D Cruzeiro, Mingning Zhu, Margaux M Pinney, Filip Yabukarski, Jason P Schwans, Todd J Martínez, Daniel Herschlag.

Enzymes exist in ensembles of states that encode the energetics underlying their catalysis. Conformational ensembles built from 1231 structures of 17 serine proteases revealed atomic-level changes across their reaction states. By comparing the enzymatic and solution reaction, we identified molecular features that provide catalysis and quantified their energetic contributions to catalysis. Serine proteases precisely position their reactants in destabilized conformers, creating a downhill energetic gradient that selectively favors the motions required for reaction while limiting off-pathway conformational states. The same catalytic features have repeatedly evolved in proteases and additional enzymes across multiple distinct structural folds. Our ensemble-function analyses revealed previously unknown catalytic features, provided quantitative models based on simple physical and chemical principles, and identified motifs recurrent in nature that may inspire enzyme design.

DOI: https://doi.org/10.1126/science.ado5068