bims-enlima Biomed News
on Engineered living materials
Issue of 2025–04–27
forty-six papers selected by
Rahul Kumar, Tallinna Tehnikaülikool



  1. Nat Commun. 2025 Apr 23. 16(1): 3832
      Natural ecosystems efficiently sequester CO2 but containing and controlling living systems remains challenging. Here, we engineer a photosynthetic living material for dual CO2 sequestration that leverages biomass production and insoluble carbonate formation via microbially induced carbonate precipitation (MICP). To achieve this, we immobilize photosynthetic microorganisms within a printable polymeric network. Digital design and fabrication of the living structures ensure sufficient light access and nutrient supply to encapsulated cyanobacteria, enabling long-term culture for over a year. We showcase that photosynthetic living materials are able to sequester 2.2 ± 0.9 mg of CO2 per gram of hydrogel material over 30 days and 26 ± 7 mg of CO2 over 400 days. These findings highlight the potential of photosynthetic living materials for scalable, low-maintenance carbon sequestration with applications in carbon-neutral infrastructure and CO2 mitigation.
    DOI:  https://doi.org/10.1038/s41467-025-58761-y
  2. ACS Appl Mater Interfaces. 2025 Apr 25.
      Cascade interactions are fundamental to enzyme catalysis and cellular activities, enabling dynamic and adaptive responses to environmental stimuli. DNA-based cascade systems have been widely employed to mimic biological processes, such as immune responses and DNAzyme catalysis, achieved mainly through the hybridization interaction. Herein, we present a cascade DNA system involving single-stranded sequences, noncanonical cofactor-bridged duplexes, and canonical duplexes to construct and dissociate hydrogel matrices. In this work, thymine-rich oligonucleotides (T-strands) exist as single-stranded random coils in a buffer at pH 7.2. Upon the introduction of a low-molecular-weight cofactor, melamine (MA), a supramolecular noncanonical configuration, termed the T-MA-T duplex, is formed. Subsequent addition of adenine-rich oligonucleotides (A-strands) to the system leads to the replacement of MA cofactors and the formation of more energetically favorable canonical A-T duplex structures. These consecutive structural transitions are further utilized as dynamic bridging elements in stimuli-responsive DNA hydrogels, facilitating liquid-hydrogel-liquid phase transitions. Moreover, we demonstrate precisely controlled release profiles of doxorubicin from the DNA hydrogel. This approach, leveraging both noncanonical and canonical DNA configurations in triggered cascade structural transitions, opens avenues for developing molecular switches, electronic nanodevices, adaptive materials, and other advanced applications.
    Keywords:  adenine; cofactor; melamine; noncanonical; thymine
    DOI:  https://doi.org/10.1021/acsami.5c01581
  3. Sci Adv. 2025 Apr 25. 11(17): eadu5905
      Organ-on-a-chip and microfluidic systems have improved the translational relevance of in vitro systems; however, current manufacturing approaches impart limitations on materials selection, non-native mechanical properties, geometric complexity, and cell-driven remodeling into functional tissues. Here, we three-dimensionally (3D) bioprint extracellular matrix (ECM) and cells into collagen-based high-resolution internally perfusable scaffolds (CHIPS) that integrate with a vascular and perfusion organ-on-a-chip reactor (VAPOR) to form a complete tissue engineering platform. We improve the fidelity of freeform reversible embedding of suspended hydrogels (FRESH) bioprinting to produce a range of CHIPS designs fabricated in a one-step process. CHIPS exhibit size-dependent permeability of perfused molecules into the surrounding scaffold to support cell viability and migration. Lastly, we implemented multi-material bioprinting to control 3D spatial patterning, ECM composition, cellularization, and material properties to create a glucose-responsive, insulin-secreting pancreatic-like CHIPS with vascular endothelial cadherin+ vascular-like networks. Together, CHIPS and VAPOR form a platform technology toward engineering full organ-scale function for disease modeling and cell replacement therapy.
    DOI:  https://doi.org/10.1126/sciadv.adu5905
  4. Acta Biomater. 2025 Apr 18. pii: S1742-7061(25)00288-0. [Epub ahead of print]
      A key challenge in hydrogel design for cell culture is replicating the cell-matrix interactions found in tissues. Cells use integrins to bind their local matrix and form adhesions in which integrins dynamically move on the cell membrane while applying significant forces to the local matrix. Identifying important biomaterial features for these interactions is challenging because it is difficult to independently adjust variables such as matrix stiffness, stress relaxation, the mobility of adhesion ligands, and the ability of these ligands to support cellular forces. In this work, we designed a hydrogel platform consisting of interpenetrating polymer networks of covalently crosslinked poly(ethylene glycol) (PEG) and self-assembled peptide amphiphiles (PA). We can tune the viscoelasticity of the hydrogel by modulating the composition of both networks. Ligand mobility can be adjusted independently of the matrix mechanical properties by attaching the arginine-glycine-aspartic acid (RGD) cell adhesion ligand to either the covalent PEG network, the dynamic PA network, or both networks at once. We find that endothelial cell adhesion formation and spreading is maximized in soft gels in which adhesion ligands are present on both the covalent and non-covalent networks. The dynamic nature of adhesion domains, coupled with their ability to exert substantial forces on the matrix, suggests that having different presentations of RGD ligands which are either mobile or capable of withstanding significant forces is needed to mimic different aspects of complex cell-matrix adhesions. These results will contribute to the design of hydrogels that better recapitulate physiological cell-matrix interactions. STATEMENT OF SIGNIFICANCE: Creating artificial environments that accurately mimic how cells interact with their surrounding matrix in natural tissues remains a fundamental challenge in biomaterials science. This study introduces a dual-network hydrogel platform that independently controls mechanical properties and adhesion ligand mobility by combining stable and dynamic polymer networks. A significant body of work has shown that matrix viscoelasticity and adhesion ligand mobility are important for cell adhesion and spreading. Our work builds on this by showing that endothelial cells function optimally when they can simultaneously engage with both mobile adhesion sites and force-resistant anchoring points, independent of matrix viscoelasticity. These insights will guide the design of more physiologically relevant hydrogels for tissue engineering applications and disease modeling.
    Keywords:  Cell adhesion; ECM; biomaterials; hydrogel
    DOI:  https://doi.org/10.1016/j.actbio.2025.04.037
  5. ACS Appl Bio Mater. 2025 Apr 22.
      Generating microgels is of critical importance in developing granular biomaterials, which have diverse emerging applications in regenerative medicine and tissue engineering. However, producing large volumes of microgels while maintaining a reasonably low population of polydispersity remains a challenge. Here, we introduce the Turbinator, a device that can be added on to the commercially available Shirasu Porous Glass (SPG) microdroplet production system to provide precise control of the local shear stresses around the porous glass droplet production head. In addition to reducing the polydispersity of droplet sizes produced using the SPG, this system allows for continuous production of droplets in inexpensive and massively scalable kerosene oil baths for industrial manufacturing applications. To validate the device, we develop finite element models to understand the local shear stresses applied and characterize the droplets produced under various operating conditions. Finally, we confirmed that this production method supports biological activity via viability and spreading assays of fibroblast cells and invasion assays in a model cancer spheroid system.
    Keywords:  droplet generator; emulsification; granular; microdroplets; microgels; multiphase; porous membrane; soft matter
    DOI:  https://doi.org/10.1021/acsabm.4c01950
  6. Angew Chem Int Ed Engl. 2025 Apr 23. e202505417
      Dynamic regulation of intermolecular interactions is essential for the creation of dynamic supramolecular materials with lifelike self-regulating functions. Yet specific ion effect, which is known to possess potent effect on intermolecular interactions, has remained unexplored for such a purpose. Here, we demonstrate our access to dynamic self-assembly of supramolecular hydrogels by orchestrating the Hofmeister effect through a simple enzymatic reaction. The involved gelators containing carboxylate moieties self-assemble into hydrogel (Gel1) at acidic pH and dissolve at basic pH. We surprisingly find that the dissolved gelators at basic pH can be driven to self-assemble into hydrogel (Gel2) by kosmotropic ions through the disruption of gelator-water interactions. By coupling to the enzymatic hydrolysis of urea, Gel1 gradually disintegrates over time because of the production of basic NH3. However, interestingly, with the accumulation of kosmotropic ions, NH4+ and CO32-, the dissolved gelators are driven to self-assemble into Gel2, realizing a self-regulating gel-sol-gel transition process. The transition rate and stiffness of Gel2 are tunable by adjusting the concentrations of urea or urease. This work may shed light on the creation of lifelike self-regulating supramolecular materials using Hofmeister effect for many enticing applications such as ion-programmed biosensing and drug delivery.
    Keywords:  Hofmeister effect; dynamic gelation; low-molecular-weight gelators; self-assembly; supramolecular chemistry
    DOI:  https://doi.org/10.1002/anie.202505417
  7. Nat Methods. 2025 Apr 22.
      Cells have distinct molecular repertoires on their surfaces and unique intracellular biomolecular profiles that play pivotal roles in orchestrating a myriad of biological responses in the context of growth, development and disease. A persistent challenge in the deep exploration of these cues has been in our inability to effectively and precisely capture the temporal and spatial characteristics of living cells. In this Perspective, we delve into techniques for temporal and two- and three-dimensional spatial omics analyses and underscore how their harmonious fusion promises to unlock insights into the dynamics and diversity of individual cells within biological systems such as tissues and organoids. We then explore four-dimensional profiling, a nascent but promising frontier that adds a temporal (fourth-dimension) component to three-dimensional omics; highlight the advancements, challenges and gaps in the field; and discuss potential strategies for further technological development.
    DOI:  https://doi.org/10.1038/s41592-025-02683-6
  8. Nat Commun. 2025 Apr 22. 16(1): 3755
      Bioelectronic devices hold transformative potential for healthcare diagnostics and therapeutics. Yet, traditional electronic implants often require invasive surgeries and  are mechanically incompatible with biological tissues. Injectable hydrogel bioelectronics offer a minimally invasive alternative that interfaces with soft tissue seamlessly. A major challenge is the low conductivity of bioelectronic systems, stemming from poor dispersibility of conductive additives in hydrogel mixtures. We address this issue by engineering doping conditions with hydrophilic biomacromolecules, enhancing the dispersibility of conductive polymers in aqueous systems. This approach achieves a 5-fold increase in dispersibility and a 20-fold boost in conductivity compared to conventional methods. The resulting conductive polymers are molecularly and in vivo degradable, making them suitable for transient bioelectronics applications. These additives are compatible with various hydrogel systems, such as alginate, forming ionically cross-linkable conductive inks for 3D-printed wearable electronics toward high-performance physiological monitoring. Furthermore, integrating conductive fillers with gelatin-based bioadhesive hydrogels substantially enhances conductivity for injectable sealants, achieving 250% greater sensitivity in pH sensing for chronic wound monitoring. Our findings indicate that hydrophilic dopants effectively tailor conducting polymers for hydrogel fillers, enhancing their biodegradability and expanding applications in transient implantable biomonitoring.
    DOI:  https://doi.org/10.1038/s41467-025-59045-1
  9. Nat Mater. 2025 Apr 23.
      Mechanical metamaterials can achieve high stiffness and strength at low densities, but often at the expense of low ductility and stretchability-a persistent trade-off in materials. In contrast, double-network hydrogels feature interpenetrating compliant and stiff polymer networks, and exhibit unprecedented combinations of high stiffness and stretchability, resulting in exceptional toughness. Here we present double-network-inspired metamaterials by integrating monolithic truss (stiff) and woven (compliant) components into a metamaterial architecture, which achieves a tenfold increase in stiffness and stretchability compared to its pure counterparts. Nonlinear computational mechanics models elucidate that enhanced energy dissipation in these double-network-inspired metamaterials stems from increased frictional dissipation due to entanglements between networks. Through introduction of internal defects, which typically degrade mechanical properties, we demonstrate a threefold increase in energy dissipation for these metamaterials via failure delocalization. This work opens avenues for developing metamaterials in a high-compliance regime inspired by polymer network topologies.
    DOI:  https://doi.org/10.1038/s41563-025-02219-5
  10. J Mater Chem B. 2025 Apr 22.
      Restoration of partial thickness chondral defects (PTCDs) may be achieved with a synthetic substitute that mimics the discrete mechanical properties of the superficial and transitional chondral layers. Moreover, innate adhesivity of the two components would enable the facile construction and integrity of this bilayered system. Herein, we report a PTCD bilayered substitute formed by triple network (TN) hydrogels that leverage electrostatic charge interactions to achieve mechanical mimicry and self-assembly. TN hydrogels were formed with a polyampholyte 3rd network of five different charge composition (i.e., ratio of cationic and anionic monomers), as well as two crosslink densities. All TN hydrogels exhibited cartilage-like hydration. A single superficial-like chondral layer TN hydrogel, with a somewhat more anionic 3rd network, was identified having mimetic compressive modulus (∼1.8 MPa) and strength (∼13 MPa). Additionally, three transitional-like chondral layer candidates were identified, including two TN hydrogels with a more cationic 3rd network in addition to the TN hydrogel with a 'cationic-only' 3rd network. The adhesivity of the superficial layer and the three transitional layer candidates was found to be robust (∼>100 kPa), wherein the bilayered construct exhibited cohesive rather than adhesive failure.
    DOI:  https://doi.org/10.1039/d5tb00050e
  11. Acta Biomater. 2025 Apr 22. pii: S1742-7061(25)00147-3. [Epub ahead of print]
      The extracellular matrix (ECM) is the body's natural cell-scaffolding material, and its structure and content are often imitated for applications in tissue engineering and regenerative medicine to promote biocompatibility. One approach toward biomimicking natural ECMs is to utilize decellularized extracellular matrices (dECMs), which involve removing cellular components from native tissues to preserve natural components. Solubilizing dECMs to produce bioinks therefore holds high potential for 3D biofabrication and bioprinting of bioactive scaffolds and tissues. However, solubilized ECMs have low printability owing to their slow gelation times, which necessitates additional artificial modifications (e.g. crosslinking) to facilitate biofabrication applications. In this study, we demonstrate a method utilizing macromolecular crowding (MMC) to confer printability, via rapid gelation, to solubilized unmodified dECMs from a variety of tissue types - heart, muscle, liver, small intestine, and large intestine. We show cell spreading and contractility in cell-laden dECM gels fabricated through MMC, highlighting biocompatibility with our method. Finally, we demonstrate successful extrusion bioprinting of complex 3D structures using unmodified dECM solutions as bioinks, revealing the potential of our MMC-based fabrication method for layer-by-layer building of user-designed bioinks made from wide-ranging fully physiological tissues. STATEMENT OF SIGNIFICANCE: Decellularized extracellular matrix (dECM) bioinks are among the most promising materials for simulating native organ-specific extracellular matrices. However, standard methods for gelling solubilized dECMs are slow and result in poor mechanical and structural characteristics, reducing printability. dECM solutions are typically supplemented with additional crosslinkers for the formation of robust hydrogels. The crosslinkers may be toxic to cells, and they often need UV light for activation. Here, we present a method that allows wide-ranging dECMs to be easily patternable and 3D printable in their unmodified forms. We demonstrate cell spreading and contractility in cell-laden unmodified dECM gels created demonstrating cell viability and bioactivity. We also demonstrated successful extrusion bioprinting of complex 3D structures utilizing low concentration unmodified dECM bioinks and normal healthy lung fibroblasts.
    Keywords:  Bioprinting; Decellularized extracellular matrix; Macromolecular crowding; PEG
    DOI:  https://doi.org/10.1016/j.actbio.2025.02.052
  12. Nature. 2025 Apr 23.
      
    Keywords:  Cell biology; Structural biology
    DOI:  https://doi.org/10.1038/d41586-025-01167-z
  13. ACS Appl Bio Mater. 2025 Apr 24.
      Mitigating the attachment of microorganisms to polymer biomaterials is critical for preventing hospital-acquired infections. Two chemical strategies to mitigate fouling include fabricating fouling-resistant surfaces, which typically present hydrophilic polymers, such as polyethylene glycol (PEG), or creating fouling-release surfaces, which are generally hydrophobic featuring polydimethylsiloxane (PDMS). Despite the demonstrated promise of employing PEG or PDMS, amphiphilic PEG/PDMS copolymer materials remain understudied. Here, for the first time, we investigated if phase-separated amphiphilic copolymers confounded microbial adhesion. We used bottlebrush amphiphilic PEG/PDMS co-networks and homopolymer networks to study bacterial adhesion across a library of gels (ϕPEG = 0.00, 0.21, 0.40, 0.55, 0.80, and 1.00). Hydrated atomic force microscopy measurements revealed that most of the gels had low surface roughness, less than 5 nm, and an elastic modulus of ∼80 kPa. Interestingly, the surface roughness and elastic modulus of the ϕPEG = 0.40 gel were twice as high as those of the other gels due to the presence of crystalline domains, as confirmed using polarized optical microscopy on the hydrated gel. The interactions of these six well-characterized gels with bacteria were determined using Escherichia coli K12 MG1655 and Staphylococcus aureus SH1000. The attachment of both microbes decreased by at least 60% on all polymer gels versus the glass controls. S. aureus adhesion peaked on the ϕPEG = 0.40, likely due to its increased elastic modulus, consistent with previous literature demonstrating that modulus impacts microbial adhesion. These findings suggest that hydrophilic, hydrophobic, and amphiphilic biomaterials effectively resist the early attachment of Gram-negative and Gram-positive microorganisms, providing guidance for the design of next-generation antifouling surfaces.
    Keywords:  amphiphilic; antifouling; bottlebrush; microorganism; polydimethylsiloxane; polyethylene glycol
    DOI:  https://doi.org/10.1021/acsabm.5c00291
  14. Am J Physiol Cell Physiol. 2025 Apr 24.
      Chemical and mechanical cues within the extracellular matrix (ECM) can initiate intracellular signaling that changes an array of fundamental cell functions. In recent work, studies of cell-ECM adhesion have deepened to include the influence of the physical ECM on cell metabolism. Since many biological processes involve metabolic programs, changes to cellular metabolism in response to cues in the ECM can have marked effects on cell health. In this review, we describe molecular mechanisms associated with cell-ECM adhesion that are key players in metabolism-induced changes to cell behaviors, including migration. We first review how changes to metabolite availability in the extracellular environment or manipulation of metabolic machinery in cells impact focal adhesions. We then connect this work to recent findings regarding the reverse relationship, namely how the manipulation of focal adhesion proteins or integrins feeds back to alter cell metabolism. Finally, we consider the latest findings from studies that describe how the mechanical properties of the ECM, primarily stiffness and confinement, alter cellular metabolism. We identify key areas of future investigation that may elucidate the molecular drivers that permit cells to respond to mechanical and chemical ECM cues by reprogramming their metabolism to better inform future diagnostics and therapeutics for disease states.
    Keywords:  Extracellular Matrix; Focal Adhesions; Integrins; Metabolism; Migration
    DOI:  https://doi.org/10.1152/ajpcell.00892.2024
  15. Nat Commun. 2025 Apr 24. 16(1): 3861
      Electrons in low-dimensional materials driven out of equilibrium by a strong electric field exhibit intriguing effects that have direct analogues in high-energy physics. In this work we demonstrate that two of these effects can be observed in graphene, leading to relevant implications for light-matter interactions at the nanoscale. For doped graphene, the Cherenkov emission of phonons caused by the fast flow of out-of-equilibrium electrons was found to induce direction-dependent asymmetric plasmon damping and an unexpected generation of photocurrent. For graphene close to charge neutrality, incident infrared photons were found to disrupt the creation-recombination balance of electron-hole pairs enabled by the condensed matter version of the Schwinger effect, resulting in an excess photocurrent that we term Schwinger photocurrent. Both Schwinger and Cherenkov photocurrents are different from other known light-to-current down conversions scenarios and thus expand the family of photoelectric effects in solid state devices. Through nano-infrared imaging methodology, we provide a more comprehensive view of current-driven nonequilibrium electrodynamics in graphene.
    DOI:  https://doi.org/10.1038/s41467-025-58953-6
  16. Soft Matter. 2025 Apr 23.
      Mechanical metamaterials have been widely studied for their broad range of exotic mechanical properties, and there is particular interest in imparting these materials with tunability to rationally alter their mechanical response on demand. Here, the concept of second-order rigidity is leveraged to design metamaterials that possess a floppy deformation mode, but that can be rigidified by altering the length of the constituent beams, such that a self-stress emerges and the floppy mode vanishes. This simple change in beam length can also give rise to controllable prestress in the material, allowing for further tuning of the elastic properties. Using a design validated with macroscopic 2D unit cells, a microfabricated 3D lattice material is demonstrated. Due to the generality of the rigidity transition, the design can be expanded to any combination of beam lengths for a given topology. Finally, a temperature-responsive hydrogel is incorporated to access the rigidity transition in situ. This design represents a simple and scalable method to assemble mechanical metamaterials with tunable rigidity.
    DOI:  https://doi.org/10.1039/d4sm01318b
  17. Annu Rev Genomics Hum Genet. 2025 Apr 25.
      The growing field of human synthetic biology has rapidly accelerated the development of programmable genetic systems that can control cellular phenotypes and function. As the scale of synthetic systems has increased, researchers have focused on identifying modular regulators that act at the levels of DNA, RNA, and protein to create synthetic control points at each level of gene expression. Expanding these assays to multiple cellular contexts has made it possible to both manipulate endogenous gene programs and create synthetic gene circuits that yield designer cell outputs. Here, we review recent advances in high-throughput human synthetic biology that have led to the development of multilevel tools for gene expression control. We highlight the development of synthetic gene programs that can both provide information on and manipulate cellular behavior and discuss the application of programmable genetic tools in therapeutic contexts to illuminate the power of these new biological approaches.
    DOI:  https://doi.org/10.1146/annurev-genom-120423-013542
  18. Nat Commun. 2025 Apr 23. 16(1): 3816
      Chromatin organization regulates gene expression, with nanoscale heterochromatin domains playing a fundamental role. Their size varies with microenvironmental stiffness and epigenetic interventions, but how these factors regulate their formation and influence transcription remains unclear. To address this, we developed a sequencing-informed copolymer model that simulates chromatin evolution through diffusion and active epigenetic reactions. Our model predicts the formation of nanoscale heterochromatin domains and quantifies how domain size scales with epigenetic reaction rates, showing that epigenetic and compaction changes primarily occur at domain boundaries. We validated these predictions via Hi-C and super-resolution imaging of hyperacetylated melanoma cells and identified differential expression of metastasis-related genes through RNA-seq. We validated our findings in hMSCs, where epigenetic reaction rates respond to microenvironmental stiffness. Conclusively, our simulations reveal that heterochromatin domain boundaries regulate gene expression and epigenetic memory. These findings demonstrate how external cues drive chromatin organization and transcriptional memory in development and disease.
    DOI:  https://doi.org/10.1038/s41467-025-59001-z
  19. Nature. 2025 Apr 23.
      
    Keywords:  Engineering; Materials science
    DOI:  https://doi.org/10.1038/d41586-025-01284-9
  20. Anal Chem. 2025 Apr 21.
      Every year, bacterial infections are responsible for over 7 million deaths globally. Timely detection and identification of these pathogens enable timely administration of antimicrobial agents, which can save thousands of lives. Most of the currently known approaches that can address these needs are time- and labor consuming. In this study, we examine the potential of innovative nano-infrared spectroscopy, also known as atomic force microscopy infrared (AFM-IR) spectroscopy, and machine learning in the identification of different bacteria. We demonstrate that a single bacteria cell is sufficient to identify Borreliella burgdorferi, Escherichia coli, Mycobacterium smegmatis, and two strains of Acinetobacter baumannii with 100% accuracy. The identification is based on the vibrational bands that originate from the components of the cell wall as well as the interior biomolecules of the bacterial cell. These results indicate that nano-IR spectroscopy can be used for the nondestructive, confirmatory, and label-free identification of pathogenic microorganisms at the single-cell level.
    DOI:  https://doi.org/10.1021/acs.analchem.5c01677
  21. Polym Chem. 2025 Feb 07. 16(5): 589-597
      Photo-mediated additive manufacturing from liquid resins (vat photopolymerization) is a rapidly growing field that will enable a new generation of electronic devices, sensors, and soft robotics. Radical-based polymerization remains the standard for photo-curing resins during the printing process due to its fast polymerization kinetics and the range of available photoinitiators. Comparatively, there are fewer examples of non-radical chemical reactions for vat photopolymerization, despite the potential for expanding the range of functional materials and devices. Herein, we demonstrate ionic liquid resins for vat photopolymerization that utilize photo-base generators (PBGs) to catalyze thiol-Michael additions as the network forming reaction. The ionic liquid increased the rate of curing, while also introducing ionic conductivity to the printed structures. Among the PBGs explored, 2-(2-nitrophenyl)-propyloxycarbonyl tetramethylguanidine (NPPOC-TMG) was the most effective for the vat photopolymerization process wherein 250 μm features were successfully printed. Lastly, we compared the mechanical properties of the PBG catalyzed thiol-Michael network versus the radical polymerized network. Interestingly, the thiol-Michael network had an overall improvement in ductility compared to the radical initiated resin, since step-growth methodologies afford more defined networks than chain growth. These ionic liquid resins for thiol-Michael additions expand the chemistries available for vat photopolymerization and present opportunities for fabricating devices such as sensors.
    Keywords:  additive manufacturing; ionic liquid; ionogel; photobase generator; thiol-Michael polymerization
    DOI:  https://doi.org/10.1039/d4py01120a
  22. Trends Biotechnol. 2025 Apr 22. pii: S0167-7799(25)00128-3. [Epub ahead of print]
      Microalgae-based oral vaccines bolster aquaculture by sustainably enhancing fish immunity and curbing disease outbreaks. Here, we introduce the rational design of vaccine antigens and discuss the oral delivery and immune benefits of microalgae-based vaccines. We expect advances in synthetic biology and fish immune metabolism to drive microalgae-based vaccine innovation.
    Keywords:  engineering biology; fish pathogen immunity; microalgae-based vaccines; oral vaccine delivery; rational design; synthetic biology
    DOI:  https://doi.org/10.1016/j.tibtech.2025.04.001
  23. Nat Commun. 2025 Apr 24. 16(1): 3856
      In the evolving landscape of scientific research, the complexity of global challenges demands innovative approaches to experimental planning and execution. Self-Driving Laboratories (SDLs) automate experimental tasks in chemical and materials sciences and the design and selection of experiments to optimize research processes and reduce material usage. This perspective explores improving access to SDLs via centralized facilities and distributed networks. We discuss the technical and collaborative challenges in realizing SDLs' potential to enhance human-machine and human-human collaboration, ultimately fostering a more inclusive research community and facilitating previously untenable research projects.
    DOI:  https://doi.org/10.1038/s41467-025-59231-1
  24. ACS Nano. 2025 Apr 25.
      The natural self-assembly tendency of proteins to build complex structural architectures has kindled inspiration in developing supramolecular structures through the rational design of biomacromolecules. While there has been significant progress in achieving precise control over the morphology of self-assembled structures, combining different molecules within assemblies enables the design of materials with increased complexity, sophisticated structures, and a broad spectrum of functionalities. Here, the development of 1D and 2D peptide-protein coassembled systems based on the design of amphiphilic peptides and engineered proteins is described. The peptide was optimized to form stable self-assembled fibers by evaluating, computationally and experimentally, the assembling tendencies and the supramolecular features of peptides with different lengths and negative charges. A superhelical repeat protein was engineered by fusing one or two amphiphilic peptides into one or both termini. This modification drove the coassembly between the self-assembled fibers and the protein with one or two peptides, resulting in 1D or 2D coassembled systems. The protein films and the 2D coassembled system exhibited high ionic conductivity for a biomolecular system, attributed to their high content of charged residues, positioning these materials as promising candidates for developing bioelectronic devices. Thus, this work provides a versatile framework for developing coassembled materials with tunable dimensionality by using biocompatible building blocks without any additional chemical moieties, highlighting the potential for their use in biocompatible electronics.
    Keywords:  conductive materials; peptide design; peptide−protein coassemblies; protein engineering; protein paracrystals; self-assembly; supramolecular fibers
    DOI:  https://doi.org/10.1021/acsnano.4c18613
  25. Stem Cell Rev Rep. 2025 Apr 21.
      The field of regenerative medicine has witnessed significant advancements in recent years, particularly in the application of biomaterials to enhance stem cell differentiation. Biomaterials serve as scaffolds that can support cellular functions and influence the fate of stem cells through biochemical and physical cues. This paper reviews recent advancements in biomaterials designed for stem cell differentiation, focusing on their composition, properties, and applications in tissue engineering. We explore various types of biomaterials, including natural polymers, synthetic polymers, hydrogels, and nanomaterials, and discuss how they can be tailored to create microenvironments that promote specific differentiation pathways. Additionally, we highlight the challenges and future directions in this rapidly evolving field.
    Keywords:  3D bioprinting; Biomaterials; Extracellular matrix; Hydrogels; Regenerative medicine; Stem cell differentiation
    DOI:  https://doi.org/10.1007/s12015-025-10879-8
  26. Soft Matter. 2025 Apr 23.
      Numerical simulations are used to study the effect of varying magnitudes of active matter force on non-vibrated and vertically vibrated gas-fluidized granular materials. We observe that if the ratio of active matter force to gravity is less than 1, but above 0, gas bubbles produced by fluidization generally increase in size which promotes mixing. However, if the ratio of active matter force to gravity exceeds 1, then the active matter force suppresses bubbling and the mixing is poorer. Furthermore, we find that if the active matter force significantly exceeds 1, the mixing can be enhanced despite no bubbling, owing to diffusion. By vertically vibrating the granular bed, and subsequently producing structured bubbling, we find that bubbles persist for larger active matter force, which we attribute to the larger bubble size observed for structured bubbling as compared to chaotic bubbling. Finally, we present a non-dimensional regime map describing the transition of sub-diffusive, diffusive, and advective transport regimes depending on the balance of active matter force to drag force to gravitational force for fluidized active granular materials.
    DOI:  https://doi.org/10.1039/d5sm00239g
  27. Sci Adv. 2025 Apr 25. 11(17): eadu4678
      Existing origami patterns can transform flat sheets into curved surfaces or be stacked into volumetric lattices with tunable properties. Their folded surfaces, however, cannot morph into other rigid states, and their three-dimensional (3D) tessellations allow stiffness tuning only through large size variations, causing abrupt shifts in stiffness and affecting other properties such as relative density. These limitations hinder their use as reprogrammable structural materials in real-life applications. Here, we introduce a reprogrammable origami integrating curved and straight bistable creases to address both challenges: attaining rigidity while allowing reversible remorphability into numerous load-bearing shapes and generating 3D curved-plate lattices, delivering in a prescribed configuration of fixed dimensions continuously tunable elastic moduli spanning two orders of magnitude. Leveraging curved origami theories, differential geometry, paperboard models, and experiments, we construct the folded pattern, formulate its geometric mechanics, and quantify its mechanical performance. Our approach provides a versatile platform for multifunctional metamaterials, enabling adaptive and resilient materials in aerospace, biomechanics, and soft robotics.
    DOI:  https://doi.org/10.1126/sciadv.adu4678
  28. Science. 2025 Apr 25. 388(6745): 415-422
      Protein polymer scaffolds composed of death fold (DF) proteins are critical to the formation of signalosomes in immune signaling. The biophysical properties that these polymeric scaffolds require for signal transduction are not clearly defined. Here, we engineered single-component DF signalosomes. We found that functionality depends on the stability provided by the DF polymer, which could also be achieved with a bacterial DF domain, a synthetic filament-forming domain, and amyloid-like sequences. This demonstrates the importance of polymer stability and inducibility irrespective of the motif's origin. By varying the number of included TRAF6 interaction motifs, we demonstrate that avidity is a tunable property that can control the amplitude of signaling outputs. This work lays out a reductionist framework to elucidate the required signaling properties through polymeric scaffolds by adjusting their assembly kinetics, stability, and avidity.
    DOI:  https://doi.org/10.1126/science.adq3234
  29. PLoS Comput Biol. 2025 Apr 24. 21(4): e1013005
      Symmetry principles play an important role in geometry, and physics, allowing for the reduction of complicated systems to simpler, more comprehensible models that preserve the system's features of interest. Biological systems are often highly complex and may consist of a large number of interacting parts. Using symmetry fibrations, the relevant symmetries for biological "message-passing" networks, we introduce a scheme, called Complexity Reduction by Symmetry or CoReSym, to reduce the gene regulatory networks of Escherichia coli and Bacillus subtilis bacteria to core networks in a way that preserves the dynamics and uncovers the computational capabilities of the network. Gene nodes in the original network that share isomorphic input trees are collapsed by the fibration into equivalence classes called fibers, whereby nodes that receive signals with the same "history" belong to one fiber and synchronize. Then we reduce the networks to its minimal computational core via k-core decomposition. This computational core consists of a few strongly connected components or "signal vortices," in which signals can cycle through. While between them, these "signal vortices" transmit signals in a feedforward manner. These connected components perform signal processing and decision making in the bacterial cell by employing a series of genetic toggle-switch circuits that store memory, plus oscillator circuits. These circuits act as the central computation device of the network, whose output signals then spread to the rest of the network. Our reduction method opens the door to narrow the vast complexity of biological systems to their minimal parts in a systematic way by using fundamental theoretical principles of symmetry.
    DOI:  https://doi.org/10.1371/journal.pcbi.1013005
  30. Nat Commun. 2025 Apr 23. 16(1): 3792
      While hierarchical ordering is a distinctive feature of natural tissues and is directly responsible for their diverse and unique properties, efforts to synthesize biomaterials have primarily focused on using molecular-based approaches with little emphasis on multiscale structure. Here, we report a bottom-up self-assembly process to produce highly porous hydrogel fibers that resemble extracellular matrices both structurally and mechanically. Physically crosslinked nanostructured micelles form the walls of micrometer-sized water-rich pores with preferred orientation along the fiber direction. Low elastic moduli (<1 kPa), high elasticity (extending by more than 12 times the initial length), non-linear elasticity (e.g., hyperelasticity), and completely reversible extension are derived from unevenly distributed strain between the micrometer-sized pores and the polymer chains, which is reminiscent of cellular solids. Control of the material microstructure and orientation over many orders of magnitude (e.g., nm-μm), while holding the nanostructure constant, reveals how the multiscale structure directly impacts mechanical properties.
    DOI:  https://doi.org/10.1038/s41467-025-59171-w
  31. Nat Commun. 2025 Apr 19. 16(1): 3728
      Programmed self-assembly of RNA nanostructures presents a strategic approach to developing biomaterials with tailored properties and functionalities. Despite advancements, the variety, complexity, and programmability of de novo engineered RNA nanostructures remain limited. Here, we introduce a category of artificially designed RNA tiles by integrating antiparallel crossovers and T-junctions, featuring a controllable angle of either 65o or 90o. A total of 22 distinct tiles are explored, significantly expanding the collection of artificially designed multi-stranded RNA tiles. We investigate the design strategies that affect array assembly including T-loop configuration, sticky end pairing, structural diversification, and variations in annealing methods. Additionally, one single-stranded TC-RNA tile is designed and folded co-transcriptionally, suggesting promising applications in synthetic biology and molecular engineering. Furthermore, we demonstrate the integration of split broccoli RNA aptamers into the multi-stranded monomer tiles, enabling fluorescence activation along linear arrays for programmable RNA sensing. The facile incorporation with RNA functional nanostructures highlights the vast potential of these RNA tiles in constructing more sophisticated nanostructures for diverse biomaterial applications.
    DOI:  https://doi.org/10.1038/s41467-025-58938-5
  32. ACS Nano. 2025 Apr 24.
      Gels with excellent mechanical properties and antifatigue-fracture capability are attractive materials for load-bearing applications; however, at extreme temperatures, they still suffer from catastrophic failure caused by freezing- or dehydration-induced crack propagation. Here, we present a series of hierarchical anisotropic composite organogels that are strong yet tough and antifatigue-fracture over a wide temperature range (-30 to 60 °C) through the combination strategies of freezing-casting, annealing, and solvent exchange with polyols. Such a hybrid design endows the gels with anisotropic and hierarchical structures and excellent tolerance to extreme temperatures, thus guaranteeing efficient energy dissipation and crack propagation resistance under both ambient and harsh conditions. For instance, the organogel obtained via solvent exchange with glycerol exhibited high strength (22.6 MPa), toughness (198.0 MJ/m3), fatigue threshold (6.92 kJ/m2), and particularly, a superhigh fracture energy (665.7 kJ/m2), which is even higher than anhydrous elastomers, metals, and alloys. Importantly, these values were further boosted at extreme temperatures, such as fatigue thresholds of 8.01 and 9.77 kJ/m2 at -30 and 60 °C, respectively. This work offers an attractive strategy for fabricating gel materials that are reliable for load-bearing applications under extreme conditions.
    Keywords:  antifatigue-fracture; extreme conditions; hydrogels; organogels; strong yet tough
    DOI:  https://doi.org/10.1021/acsnano.5c01482
  33. Proc Natl Acad Sci U S A. 2025 Apr 29. 122(17): e2417452122
      Plasmid conjugation is a contact-dependent horizontal gene transfer mechanism that significantly contributes to the dissemination of antibiotic resistance among bacteria. While the molecular mechanisms of conjugation have been extensively studied, our understanding of plasmid transfer dynamics within spatially structured bacterial communities and the influence of community architecture on plasmid dissemination remains limited. In this study, we use live-cell fluorescence microscopy to investigate the propagation of the broad host range RP4 conjugative plasmid in Escherichia coli populations exhibiting varying levels of spatial organization. In high-density, two-dimensional cell monolayers, direct and tight contact between donors and recipients is not only necessary but also sufficient to trigger RP4 plasmid transfer, ensuring optimal plasmid propagation. In three-dimensional mature biofilms, the emergent community architecture limits the ability of donor cells to enter regions with high cell density, which hinders the establishment of direct contacts with recipients and impedes plasmid transfer in biofilms. In contrast, microcolonies, early-stage biofilms, and biofilms with a lower surface coverage leave open access points for donor cells in regions that later emerge as high-cell-density regions in mature biofilms, which facilitates plasmid transfer. These findings reveal the crucial role of bacterial community architecture in determining the efficiency of plasmid dissemination.
    Keywords:  antibiotic resistance; bacterial conjugation; biofilm; horizontal gene transfer; live-cell fluorescence microscopy
    DOI:  https://doi.org/10.1073/pnas.2417452122
  34. Small. 2025 Apr 24. e2412657
      Modulating the mechanical properties of soft materials with light is essential for achieving customizable functionalities. However, existing photo-responsive materials suffer from limited mechanical performance and a restricted tunable range. Here, a photo-tunable elastomer is developed by incorporating a urethane acrylate network with selenosulfide-based dynamic covalent crosslinkers, achieving high tensile strength exceeding 1.2 MPa in their stiff state and variable Young's modulus within a 0.8 MPa range. These crosslinkers undergo selenosulfide photo-metathesis, gradually breaking under ultraviolet light and reforming under visible light, enabling fine control over the modulus, strength, and stretchability of the elastomer. In terms of controllability, the design supports multiple tunable states, which allow for the use of intermediate mechanical properties. Moreover, by modeling the crosslinking density changes with reaction kinetics, modulus variation is predicted as a function of light exposure time. The light-induced modulation facilitates localized mechanical property adjustments, generating transformable multi-material structures and enhancing fracture resistance. Integrating these crosslinkers into different polymer networks provides a strategy for creating various photo-tunable elastomers and gels.
    Keywords:  crosslinker; elastomer; mechanical property modulation; photo‐tuning; selenosulfide; urethane acrylate
    DOI:  https://doi.org/10.1002/smll.202412657
  35. NPJ Regen Med. 2025 Apr 22. 10(1): 21
      Despite the therapeutic potential of mesenchymal stromal cells (MSC), there is limited understanding of optimal extracellular matrix (ECM) environments to manufacture these cells. We developed tissue chips to study the effects of multi-factorial ECM environments under manufacturable stiffness ranges and multi-component ECM compositions. Manufacturing qualities of cell expansion potential, immunomodulation, and differentiation capacity were examined. The results show stiffness effects, with 900 kPa substrates supporting higher proliferation and osteogenic differentiation, along with anti-inflammatory IL-10 expression, whereas 150 kPa substrates promoted adipogenic differentiation at 150 kPa, suggesting that optimal ECM environments may differ based on manufacturing goals. ECM biochemistries containing fibronectin and laminin further modulated MSC manufacturing qualities across various stiffnesses. Proteomic and transcriptomic analyses revealed unique ECM combinations that induced higher levels of angiogenic and immunomodulatory cytokines, compared to single factor ECMs. These findings demonstrate that optimized ECM environments enhance MSC manufacturing quality.
    DOI:  https://doi.org/10.1038/s41536-025-00408-z
  36. Proc Natl Acad Sci U S A. 2025 Apr 29. 122(17): e2414342122
      Genome modification is essential for studying and engineering bacteria, yet making efficient modifications to most species remains challenging. Bacteriophage-encoded single-stranded DNA-annealing proteins (SSAPs) can facilitate efficient genome editing by homologous recombination, but their typically narrow host range limits broad application. Here, we demonstrate that a single library of 227 SSAPs enables efficient genome-editing across six diverse bacteria from three divergent classes: Actinomycetia (Mycobacterium smegmatis and Corynebacterium glutamicum), Alphaproteobacteria (Agrobacterium tumefaciens and Caulobacter crescentus), and Bacilli (Lactococcus lactis and Staphylococcus aureus). Surprisingly, the most effective SSAPs frequently originated from phyla distinct from their bacterial hosts, challenging the assumption that phylogenetic relatedness is necessary for recombination efficiency, and supporting the value of a large unbiased library. Across these hosts, the identified SSAPs enable genome modifications requiring efficient homologous recombination, demonstrated through three examples. First, we use SSAPs with Cas9 in C. crescentus to introduce single amino acid mutations with >70% efficiency. Second, we adapt SSAPs for dsDNA editing in C. glutamicum and S. aureus, enabling one-step gene knockouts using PCR products. Finally, we apply SSAPs for multiplexed editing in S. aureus to precisely map the interaction between a conserved protein and a small-molecule inhibitor. Overall, this library-based SSAP screen expands engineering capabilities across diverse, previously recalcitrant microbes, enabling efficient genetic manipulation for both fundamental research and biotechnological applications.
    Keywords:  SSAP; genome editing; microbiology; recombineering; reverse genetics
    DOI:  https://doi.org/10.1073/pnas.2414342122
  37. Nature. 2025 Apr;640(8060): 884-885
      
    Keywords:  Applied physics; Materials science; Technology
    DOI:  https://doi.org/10.1038/d41586-025-01131-x
  38. J Am Chem Soc. 2025 Apr 24.
      Glycans are intrinsically flexible molecules that can adopt many conformations. These molecules often carry ionic functional groups that influence glycan's conformational preferences, dynamics, and aggregation tendencies. Inspired by these mechanisms, we have engineered a glycan sequence whose secondary structure can be precisely manipulated by using ionic groups. We strategically incorporated ionic substituents into a glycan sequence adopting a hairpin conformation. Complementary ionic groups stabilized the closed conformers, while ionic repulsions shifted the populations toward the open forms. External stimuli, such as pH variations or enzyme addition, enabled us to dynamically control the hairpin's opening and closing. Additionally, changes in protonation states led to glycan aggregation, suggesting opportunities for the creation of responsive glycan-based materials.
    DOI:  https://doi.org/10.1021/jacs.4c17992
  39. ACS Appl Mater Interfaces. 2025 Apr 23.
      Natural wood has long inspired the development of artificial biomimetic and bioinspired materials aimed at enhancing human life. However, a major challenge lies in developing straightforward and versatile approaches for producing high-performance, porous wood-derived materials. In this work, we introduce a space-confined porogen photochemistry strategy for engineering wood-derived porous hydrogel composites. Under light irradiation, the nitrogen gas release and the liquid precursor rapidly solidify into hydrogels within 30 s, facilitating in situ pore formation within the wood template. The integration of aligned wood structures with hydrogel multinetworks yields a composite material capable of sustaining a maximum stress of 7 MPa at a critical strain of 200%, with a high porosity of 70%. The anisotropic nature enhances directional ion transport and sensing with performance further tunable by adjusting porosity. This capability positions these materials as promising candidates for flexible zinc-air batteries, which demonstrate a higher output voltage and power density. Additionally, the superior mechanical integrity and water-retention abilities extend the battery life (up to ∼120 h) and support flexibility, as shown by 1000 cycles in bending tests. This space-confined porogen photochemistry approach and the resulting wood-derived composites are poised to make a significant impact in fields spanning energy storage, sensing technologies, and beyond.
    Keywords:  orthogonal photochemistry; porous hydrogel; tough hydrogel; wood composite
    DOI:  https://doi.org/10.1021/acsami.5c04248
  40. Adv Sci (Weinh). 2025 Apr 25. e2410539
      Conventional devices lack the adaptability and responsiveness inherent in the design of nature. Therefore, they cannot autonomously maintain themselves in natural environments. This limitation is primarily because of using rigid and fragile material components for their construction, which hinders their ability to adapt and evolve in changing environments. Moreover, they often cannot self-repair after injuries or significant damage. Even devices with self-healing, soft, and responsive properties often fail to seamlessly integrate all these attributes into a single, scalable, and cohesive platform. In this study, a significant breakthrough is introduced by utilizing graphene-poly(3,4-ethylenedioxythiophene): polystyrene sulfonate (graphene-PEDOT:PSS) fillers to transform a typically weak, insulating, and jelly-like material into a soft electronic material with properties akin to those of living organisms, such as skin tissue. The developed electronic materials exhibit a range of other capabilities attributed to the hierarchical organization originating from filler enhancement, which includes methods such as heat regulation, 3D printability, and multiplex sensing. The introduction of this new class of materials can facilitate the self-maintenance of life-like soft robots and bioelectronics that can be seamlessly integrated within dynamic environments, such as the human body, while demonstrating the ability to sense, respond, and adapt to challenging environments.
    Keywords:  adaptive robotics; bioelectronics; graphene‐PEDOT; self‐healing materials; soft electronics
    DOI:  https://doi.org/10.1002/advs.202410539
  41. Lab Chip. 2025 Apr 24.
      Organoid models are invaluable for studying organ processes in vitro, offering an unprecedented ability to replicate organ function. Despite recent advancements that have increased their cellular complexity, organoids generally lack key specialized cell types, such as neurons, limiting their ability to fully model organ function and dysfunction. Innervating organoids remains a significant challenge due to the asynchronous biological cues governing neural and organ development. Here, we present a versatile organ-on-a-chip platform designed to innervate organoids across diverse tissue types. Our strategy enables the development of innervated granular hydrogel tissue constructs, followed by the sequential addition of organoids. The microfluidic device features an open tissue chamber, which can be easily manipulated using standard pipetting or advanced bioprinting techniques. Engineered to accommodate microgels of any material larger than 50 μm, the chamber provides flexibility for constructing customizable hydrogel environments. Organoids and other particles can be precisely introduced into the device at any stage using aspiration-assisted bioprinting. To validate this platform, we demonstrate the successful growth of primary mouse superior cervical ganglia (mSCG) neurons and the platform's effectiveness in innervating prostate cancer spheroids and patient-derived renal cell carcinoma organoids. This platform offers a robust and adaptable tool for generating complex innervated organoids, paving the way for more accurate in vitro models of organ development, function, and disease.
    DOI:  https://doi.org/10.1039/d5lc00134j
  42. Nature. 2025 Apr;640(8060): 931-940
      Metamaterials with multimodal deformation mechanisms resemble machines1,2, especially when endowed with autonomous functionality. A representative architected assembly, with tunable chirality, converts linear motion into rotation3. These chiral metamaterials with a machine-like dual modality have potential use in areas such as wave manipulation4, optical activity related to circular polarization5 and chiral active fluids6. However, the dual motions are essentially coupled and cannot be independently controlled. Moreover, they are restricted to small deformation, that is, strain ≤2%, which limits their applications. Here we establish modular chiral metamaterials, consisting of auxetic planar tessellations and origami-inspired columnar arrays, with decoupled actuation. Under single-degree-of-freedom actuation, the assembly twists between 0° and 90°, contracts in-plane up to 25% and shrinks out-of-plane more than 50%. Using experiments and simulations, we show that the deformation of the assembly involves in-plane twist and contraction dominated by the rotating-square tessellations and out-of-plane shrinkage dominated by the tubular Kresling origami arrays. Moreover, we demonstrate two distinct actuation conditions: twist with free translation and linear displacement with free rotation. Our metamaterial is built on a highly modular assembly, which enables reprogrammable instability, local chirality control, tunable loading capacity and scalability. Our concept provides routes towards multimodal, multistable and reprogrammable machines, with applications in robotic transformers, thermoregulation, mechanical memories in hysteresis loops, non-commutative state transition and plug-and-play functional assemblies for energy absorption and information encryption.
    DOI:  https://doi.org/10.1038/s41586-025-08851-0
  43. Mol Cell. 2025 Apr 18. pii: S1097-2765(25)00305-3. [Epub ahead of print]
      To achieve system-level insights into proteome organization, regulation, and function, we developed an approach to generate complex cell pools with endogenously tagged proteins amenable to high-throughput visualization and perturbation. Pooled imaging coupled to in situ barcode sequencing identified the subcellular localization of each HaloTag-tagged protein, and subsequent ligand-induced misfolding of the library followed by single-cell RNA sequencing revealed responses to spatially restricted protein misfolding. These datasets characterized protein quality control responses in previously uninterrogated cellular compartments, and cross-compartment analyses revealed mutually exclusive rather than collaborative responses, whereby the heat shock response (HSR) is induced in some compartments and repressed in others where autophagy genes are induced. We further assign protein quality control functions to previously uncharacterized genes based on shared transcriptional responses to protein misfolding across cellular compartments. Altogether, we present an efficient method for large-scale studies of proteome dynamics, function, and homeostasis.
    Keywords:  hydrophobic targeting; in situ sequencing; pooled tagging; protein localization; protein misfolding; proteostasis
    DOI:  https://doi.org/10.1016/j.molcel.2025.04.002
  44. Mater Horiz. 2025 Apr 23.
      Our Emerging Investigator Series features exceptional work by early-career researchers working in the field of materials science.
    DOI:  https://doi.org/10.1039/d5mh90050f
  45. ACS Appl Bio Mater. 2025 Apr 24.
      Alginate biopolymers were modified with norbornene (Nb) and tetrazine (Tz) functional groups to generate hydrogel networks with tunable ionic and covalent cross-linking for modeling the strain-stiffening behavior of extracellular matrix. The mechanical properties of the hydrogels were investigated by oscillatory shear rheology, axial compression, and stress relaxation analysis. Introducing Nb-Tz irreversible covalent cross-links yielded dual-cross-linked hydrogels with stiffer and more elastic properties compared to purely ionically cross-linked alginate networks. The strain stiffening effect was observed under both shear amplitude sweeps and stepwise axial compression tests for the dual-cross-linked hydrogels. This study provides valuable insights into the structure-property relationship of dual-cross-linked biopolymer hydrogels for designing tunable extracellular matrix mimics of fibrotic tissues.
    Keywords:  alginate; click chemistry; dual-cross-linking; hydrogel; mechanical properties
    DOI:  https://doi.org/10.1021/acsabm.5c00094
  46. Cell Rep Methods. 2025 Apr 14. pii: S2667-2375(25)00065-7. [Epub ahead of print] 101029
      The heterochromatin protein HP1α (heterochromatin protein 1 alpha) phase separates in vitro and displays properties compatible with phase separation in cells. Phase separation of HP1α in cells is typically studied using genetically encoded fluorescent tags such as green fluorescent protein (GFP). Whether such tags affect the intrinsic phase separation properties of HP1α is understudied. We assessed how tag size and linker length affect phase separation by HP1α in vitro. GFP tags inhibited phase separation by HP1α. In contrast, an UnaG tag with a 16 amino acid glycine-glycine-serine (GGS) linker minimally perturbed HP1α phase separation in vitro and could be used to visualize HP1α dynamics in cells. We further investigated the effects of a commonly used crowding agent, polyethylene glycol (PEG). PEG induced phase separation of proteins with no propensity to phase separate under physiological buffer conditions and dampened the effects of HP1α mutations. Therefore, phase separation of biological macromolecules with PEG-containing crowding agents should be interpreted with caution.
    Keywords:  CP: Molecular biology; genetically encoded fluorescent tags; heterochromatin protein 1; liquid-liquid phase separation; microscopy
    DOI:  https://doi.org/10.1016/j.crmeth.2025.101029