bims-ecemfi Biomed News
on ECM and fibroblasts
Issue of 2025–08–31
eighteen papers selected by
Badri Narayanan Narasimhan, University of California, San Diego
  1. Hydrogel Network Architecture Design Space: Impact on Mechanical and Viscoelastic Properties.
  2. CAF-Driven Mechanotransduction via Collagen Remodeling Accelerates Tumor Cell Cycle Progression.
  3. Coupled Dynamics in Phenotype and Tissue Spaces Shape the Three-Dimensional Cancer Invasion.
  4. Cancer Microenvironment-Stimulated Mesenchymal Stem Cells in an Indirect Co-Culture System Influence Cancer Cell Growth and Apoptosis.
  5. An engineered glioblastoma model yields macrophage-secreted drivers of invasion.
  6. Viscoelasticity of Fibrous Hydrogels Driven by Dynamic Intrafibrillar Imine Cross-Linking.
  7. Bioorthogonal Engineering of Cellular Microenvironments Using Isonitrile Ligations.
  8. Using High-Throughput Screening to Identify Crosslinking Peptides That Control Cell-Mediated Matrix Degradation.
  9. Mechanical confinement governs phenotypic plasticity in melanoma.
  10. Viscoelastic Hydrogel with Mechanomodulatory Tension Shielding and Time-Dependent Immunomodulatory Effects for Scarless Healing.
  11. Engineering kidney developmental trajectory using culture boundary conditions.
  12. Cell mechanics, environmental geometry, and cell polarity control cell-cell collision outcomes.
  13. Matrix-induced nuclear remodeling and mechano-therapeutics.
  14. Continuous pore size gradient enhances zonal-specific differentiation of stem cells in an osteochondral scaffold.
  15. Accelerated maturation of branched organoids confined in collagen droplets.
  16. Tumor cell-adipocyte gap junctions activate lipolysis and contribute to breast tumorigenesis.
  17. Impact of 3D cell culture hydrogels derived from basement membrane extracts or nanofibrillar cellulose on CAR-T cell activation.
  18. Soft porous metamaterials using inflation-induced buckling for smart actuation.
  1. Gels. 2025 Jul 30. pii: 588. [Epub ahead of print]11(8):
    Hydrogel Network Architecture Design Space: Impact on Mechanical and Viscoelastic Properties.
    Andres F Roca-Arroyo, Jhonatan A Gutierrez-Rivera, Logan D Morton, David A Castilla-Casadiego.
      This comprehensive review explores the expansive design space of network architectures and their significant impact on the mechanical and viscoelastic properties of hydrogel systems. By examining the intricate relationships between molecular structure, network connectivity, and resulting bulk properties, we provide critical insights into rational design strategies for tailoring hydrogel mechanics for specific applications. Recent advances in sequence-defined crosslinkers, dynamic covalent chemistries, and biomimetic approaches have significantly expanded the toolbox for creating hydrogels with precisely controlled viscoelasticity, stiffness, and stress relaxation behavior-properties that are crucial for biomedical applications, particularly in tissue engineering and regenerative medicine.
    Keywords:  biomimetic; crosslinker architecture; extracellular matrix mimic; hydrogel; structure–property relationships; viscoelasticity
    DOI:  https://doi.org/10.3390/gels11080588
  2. Gels. 2025 Aug 13. pii: 642. [Epub ahead of print]11(8):
    CAF-Driven Mechanotransduction via Collagen Remodeling Accelerates Tumor Cell Cycle Progression.
    Yating Xiao, Yingying Jiang, Ting Bao, Xin Hu, Xiang Wang, Xiaoning Han, Linhong Deng.
      Cancer-associated fibroblasts (CAFs) restructure collagen hydrogels via actomyosin-driven fibril bundling and crosslinking, increasing polymer density to generate mechanical stress that accelerates tumor proliferation. Conventional hydrogel models lack spatial heterogeneity, thus obscuring how localized stiffness gradients regulate cell cycle progression. To address this, we developed a collagen hydrogel-based microtissue platform integrated with programmable microstrings (single/double tethering), enabling real-time quantification of gel densification mechanics and force transmission efficiency. Using this system combined with FUCCI cell cycle biosensors and molecular perturbations, we demonstrate that CAF-polarized contraction increases hydrogel stiffness (350 → 775 Pa) and reduces pore diameter (5.0 → 1.9 μm), activating YAP/TAZ nuclear translocation via collagen-integrin-actomyosin cascades. This drives a 2.4-fold proliferation increase and accelerates G1/S transition in breast cancer cells. Pharmacological inhibition of YAP (verteporfin), actomyosin (blebbistatin), or collagen disruption (collagenase) reversed mechanotransduction and proliferation. Partial rescue upon CYR61 knockdown revealed compensatory effector networks. Our work establishes CAF-remodeled hydrogels as biomechanical regulators of tumor growth and positions gel-based mechanotherapeutics as promising anti-cancer strategies.
    Keywords:  G1/S transition; YAP/TAZ; cancer-associated fibroblasts; collagen hydrogels; matrix stiffening; mechanotransduction
    DOI:  https://doi.org/10.3390/gels11080642
  3. PRX Life. 2024 Dec;pii: 043022. [Epub ahead of print]2(4):
    Coupled Dynamics in Phenotype and Tissue Spaces Shape the Three-Dimensional Cancer Invasion.
    Austin Naylor, Maximilian Libmann, Izabel Raab, Wouter-Jan Rappel, Bo Sun.
      The metastasis of solid tumors hinges on cancer cells navigating through complex three-dimensional tissue environments, characterized by mechanical heterogeneity and biological diversity. This process is closely linked to the dynamic migration behavior exhibited by cancer cells, which dictates the invasiveness of tumors. In our study, we investigate tumor spheroids composed of breast cancer cells embedded in three-dimensional (3D) collagen matrices. Through a combination of quantitative experiments, artificial-intelligence-driven image processing, and mathematical modeling, we uncover rapid transitions in cell phenotypes and phenotype-dependent motility among disseminating cells originating from tumor spheroids. Persistent invasion leads to continuous remodeling of the extracellular matrix surrounding the spheroids, altering the landscape of migration phenotypes. Consequently, filopodial cells emerge as the predominant phenotype across diverse extracellular matrix conditions. Our findings unveil the complex mesoscale dynamics of invading tumor spheroids, shedding light on the complex interplay between migration phenotype plasticity, microenvironment remodeling, and cell motility within 3D extracellular matrices.
    DOI:  https://doi.org/10.1103/prxlife.2.043022
  4. Adv Biol (Weinh). 2025 Aug 23. e00291
    Cancer Microenvironment-Stimulated Mesenchymal Stem Cells in an Indirect Co-Culture System Influence Cancer Cell Growth and Apoptosis.
    Pragati Sharma, Jun Nakanishi, Subha Narayan Rath.
      Mesenchymal stem cells (MSCs) migrate to injured tissues, aiding tissue repair, remodeling, and wound healing. As tumors are often considered to have traits of "injured tissues," MSCs are recruited to tumor microenvironments where they can have pro- and antitumorigenic influences. This study assesses whether human mesenchymal stem cells (hMSCs) of shared ancestry exhibit similar tumorigenic properties. Bone marrow-derived (hBM-MSCs) and umbilical cord-derived (hUC-MSCs) MSCs embedded in collagen are cultured in conditioned media from lung adenocarcinoma (A549) cells to mimic the extracellular matrix and soluble cues of the cancer microenvironment. Cell viability, proliferation, and immunofluorescence analyses evaluate MSC behavior under these conditions. Further, A549 cells are exposed to conditioned media from cancer-stimulated MSCs to simulate indirect co-culture, and their response is assessed through viability, immunofluorescence, and flow cytometric analysis. Results show increased viability and proliferation of hBM-MSCs, morphological changes, and elevated alpha-smooth muscle actin expression, suggesting a transition toward cancer-associated fibroblasts. In contrast, hUC-MSCs display reduced viability and no morphological alterations. Conditioned media from cancer-exposed hUC-MSCs induce apoptosis in A549 cells, whereas hBM-MSCs support A549 growth. These findings demonstrate that, despite their common origin, hUC-MSCs and hBM-MSCs exhibit opposing responses to tumor cues and influence lung cancer cell behavior differently.
    Keywords:  cancer‐associated fibroblasts; conditioned media; extracellular matrix; lung cancer; mesenchymal stem cells; tumor microenvironment
    DOI:  https://doi.org/10.1002/adbi.202500291
  5. JCI Insight. 2025 Aug 22. pii: e181903. [Epub ahead of print]10(16):
    An engineered glioblastoma model yields macrophage-secreted drivers of invasion.
    Erin A Akins, Dana Wilkins, Zaki Abou-Mrad, Kelsey Hopland, Robert C Osorio, Kenny Kh Yu, Manish K Aghi, Sanjay Kumar.
      While the accumulation of tumor-associated macrophages (TAMs) in glioblastoma (GBM) has been well documented, targeting TAMs has thus far yielded limited clinical success in slowing GBM progression due, in part, to an incomplete understanding of TAM function. Using an engineered 3D hydrogel-based model of the brain tumor microenvironment (TME), we show that M2-polarized macrophages stimulate transcriptional and phenotypic changes in GBM stem cells (GSCs) closely associated with the highly aggressive and invasive mesenchymal subtype. By combining proteomics with GBM patient single-cell transcriptomics, we identify multiple TAM-secreted proteins with putative proinvasive functions and validate TGF-β induced (TGFBI, also known as BIGH3) as a targetable TAM-secreted tumorigenic factor. Our work highlights the utility of coupling multiomics analyses with engineered TME models to investigate TAM-cancer cell crosstalk and offers insights into TAM function to guide TAM-targeting therapies.
    Keywords:  Brain cancer; Extracellular matrix; Immunology; Macrophages; Oncology
    DOI:  https://doi.org/10.1172/jci.insight.181903
  6. Biomacromolecules. 2025 Aug 20.
    Viscoelasticity of Fibrous Hydrogels Driven by Dynamic Intrafibrillar Imine Cross-Linking.
    Zheyuan Miao, Zhengkun Chen, Elizaveta Gusarova, Yingshan Ma, Eugenia Kumacheva.
      Viscoelasticity of biological fibrous networks impacts cell fates and may reflect pathological conditions in vivo. Imine-cross-linked fibrous hydrogels can serve as effective in vitro models for studying viscoelastic properties of biological tissues; however, the specific role of intrafibrillar dynamic covalent bonds in governing hydrogel elasticity and stress relaxation remains unexplored. Here, for fibrous hydrogels derived from cellulose nanocrystals and polyethylene glycol, we systematically varied the content of intrafibrillar imine cross-links to explore their impact on hydrogels' elastic response, stress relaxation, and fibrous structure. We showed that higher imine group contents resulted in greater elastic moduli and higher degrees of stress relaxation in fibrous hydrogels. The fibrous structure did not significantly change with varying imine group contents, which enabled the decoupling of changes in hydrogel morphology and viscoelastic properties. This work provides the capability of designing fibrous hydrogels with controlled viscoelasticity and exploring their roles in bioengineering.
    DOI:  https://doi.org/10.1021/acs.biomac.5c01337
  7. Adv Funct Mater. 2025 May 30. pii: 2422047. [Epub ahead of print]
    Bioorthogonal Engineering of Cellular Microenvironments Using Isonitrile Ligations.
    Ping Zhou, Lauren Brown, Christopher M Madl.
      Hydrogels are routinely used as scaffolds to mimic the extracellular matrix for tissue engineering. However, common strategies to covalently crosslink hydrogels employ reaction conditions with potential off-target biological reactivity. The limited number of suitable bioorthogonal chemistries for hydrogel crosslinking restricts how many material properties can be independently addressed to control cell fate. To expand the bioorthogonal toolkit available for hydrogel crosslinking, we identify isonitrile ligations as a promising class of reactions. Isonitriles are compact, stable, selective, and biocompatible moieties that react with chlorooxime (ChO), tetrazine (Tz), and azomethine imine (AMI) functional groups under physiological conditions. We demonstrate that all three ligation reactions can form hydrogels, with isonitrile-ChO ligation exhibiting optimal gelation properties. Synthetic poly(ethylene glycol) (PEG) hydrogels crosslinked by isonitrile-ChO ligation exhibit rapid gelation kinetics, elastic mechanical properties, stability under physiological conditions, and high biocompatibility. By combining ChO-functionalized multi-arm PEGs with isonitrile-functionalized engineered elastin-like proteins (ELPs), we demonstrate simultaneous control over network connectivity and adhesive ligand presentation, which in turn regulate cell spreading. These hydrogels enable the long-term culture of numerous human cell types relevant to regenerative medicine. Furthermore, we demonstrate that isonitrile-ChO ligation is orthogonal to common azide-alkyne cycloaddition, enabling independent, bioorthogonal functionalization of hydrogels containing live cells.
    Keywords:  bioorthogonal chemistry; engineered extracellular matrices; hydrogels; isonitrile ligation; recombinant protein materials
    DOI:  https://doi.org/10.1002/adfm.202422047
  8. Adv Healthc Mater. 2025 Aug 25. e01932
    Using High-Throughput Screening to Identify Crosslinking Peptides That Control Cell-Mediated Matrix Degradation.
    Yingjie Wu, Samuel J Rozans, Abolfazl Salehi Moghaddam, E Thomas Pashuck.
      Cells modify the extracellular matrix by expressing proteases that degrade matrix proteins, enabling cell migration within tissues. This process is mimicked in hydrogels through protease-degradable peptide crosslinks. However, cleaving hydrogel crosslinks reduces local matrix mechanical properties, and most crosslinking peptides, including the widely used GPQGIWGQ "PanMMP" sequence, often lead to bulk hydrogel degradation. Membrane-type proteases are localized to the cell surface, have important roles in cell migration, and are active in the pericellular region. To identify peptides primarily cleaved by membrane-type proteases, an approach is developed that couples proteomic identification of candidate peptides with mass spectrometry-based functional assays to quantify degradation. The target sequence is then optimized using a split-and-pool synthesis to generate over 300 peptide variants to improve degradation behavior. The optimized peptide, KLVADLMASAE, shows reduced degradation by soluble proteases, while enabling endothelial and stem cell spreading and viability comparable to PanMMP hydrogels. KLVADLMASAE-crosslinked hydrogels have reduced crosslinker degradation, are stiffer during culture, and exhibit less macroscopic degradation after 14 days of culture than PanMMP gels. The performance of KLVADLMASAE-crosslinked gels is significantly improved from the initial peptide target, validating this functional high-throughput approach for identifying peptides that control matrix degradation.
    Keywords:  cell‐matrix interactions; endothelial cells; high‐throughput; hydrogels; mesenchymal stem cells; proteases
    DOI:  https://doi.org/10.1002/adhm.202501932
  9. Nature. 2025 Aug 27.
    Mechanical confinement governs phenotypic plasticity in melanoma.
    Miranda V Hunter, Eshita Joshi, Sydney Bowker, Emily Montal, Yilun Ma, Young Hun Kim, Zhifan Yang, Laura Tuffery, Zhuoning Li, Eric Rosiek, Alexander Browning, Reuben Moncada, Itai Yanai, Helen Byrne, Mara Monetti, Elisa de Stanchina, Pierre-Jacques Hamard, Richard P Koche, Richard M White.
      Phenotype switching is a form of cellular plasticity in which cancer cells reversibly move between two opposite extremes: proliferative versus invasive states1,2. Although it has long been hypothesized that such switching is triggered by external cues, the identity of these cues remains unclear. Here we demonstrate that mechanical confinement mediates phenotype switching through chromatin remodelling. Using a zebrafish model of melanoma coupled with human samples, we profiled tumour cells at the interface between the tumour and surrounding microenvironment. Morphological analysis of interface cells showed elliptical nuclei, suggestive of mechanical confinement by the adjacent tissue. Spatial and single-cell transcriptomics demonstrated that interface cells adopted a gene program of neuronal invasion, including the acquisition of an acetylated tubulin cage that protects the nucleus during migration. We identified the DNA-bending protein HMGB2 as a confinement-induced mediator of the neuronal state. HMGB2 is upregulated in confined cells, and quantitative modelling revealed that confinement prolongs the contact time between HMGB2 and chromatin, leading to changes in chromatin configuration that favour the neuronal phenotype. Genetic disruption of HMGB2 showed that it regulates the trade-off between proliferative and invasive states, in which confined HMGB2high tumour cells are less proliferative but more drug-resistant. Our results implicate the mechanical microenvironment as a mechanism that drives phenotype switching in melanoma.
    DOI:  https://doi.org/10.1038/s41586-025-09445-6
  10. Adv Healthc Mater. 2025 Aug 20. e01954
    Viscoelastic Hydrogel with Mechanomodulatory Tension Shielding and Time-Dependent Immunomodulatory Effects for Scarless Healing.
    Chen-Hsiang Kuan, Yi-Ning Wang, En-Feng Liao, Wei-Hung Wang, Pin-Jui Kung, Wei-Yuan Huang, Shih-Heng Chen, Shih-Hsien Chen, Jin-Jia Hu, Sung-Jan Lin, Tzu-Wei Wang.
      Wound healing is a complex process that, when disrupted, can result in hypertrophic scars or keloids, causing significant physical and psychological discomfort. Despite advances in understanding fibrotic scar formation, achieving scarless healing remains challenging. Inspired by fetal wound healing, this research aims to develop a viscoelastic hydrogel mimicking fetal extracellular matrix properties. The hydrogel comprises hyaluronic acid and alginate, forming reversible dynamic Schiff base and ionic bonds. Interleukin-10 (IL-10), an anti-inflammatory cytokine, is encapsulated using polyelectrolyte complex nanoparticles (PCNs), allowing sustained release and mitigating scar formation by inhibiting inflammatory responses. The results show that this hydrogel demonstrates stress relaxation and self-healing abilities, mimicking the natural characteristics of the extracellular matrix. Additionally, cross-linking with calcium ions induces spontaneous hydrogel contraction, facilitating wound closure and providing tension shielding around the wound site. Such action effectively relieves stress in the wound milieu, reducing the likelihood of fibroblasts differentiation into myofibroblasts and preventing excessive collagen deposition. The viscoelastic hydrogel significantly enhances wound healing by integrating immunomodulatory and tension-shielding properties, thereby creating an optimal environment for scarless healing.
    Keywords:  immunomodulation; scarless healing; tension shielding; tissue engineering; viscoelastic hydrogel
    DOI:  https://doi.org/10.1002/adhm.202501954
  11. Nat Commun. 2025 Aug 22. 16(1): 7829
    Engineering kidney developmental trajectory using culture boundary conditions.
    Aria Zheyuan Huang, Louis S Prahl, Karen Xu, Robert L Mauck, Jason A Burdick, Alex J Hughes.
      Kidney explants are traditionally cultured at air-liquid interfaces, which disrupts 3D tissue structure and limits interpretation of developmental data. Here we develop a 3D culture technique using hydrogel embedding to capture kidney morphogenesis in real time. 3D culture better approximates in vivo-like niche spacing and tubule dynamics, as well as branching defects under control conditions and GDNF-RET signaling perturbations. To isolate the effect of material properties on explant development, we apply acrylated hyaluronic acid hydrogels that allow independent tuning of stiffness and adhesion. We find that sufficient stiffness and adhesive ligands are both required to maintain kidney shape. More adhesive hydrogels increase nephrons per ureteric bud (UB) tip while matrix stiffness has a "Goldilocks effect" centered at ~2 kPa. Our technique captures large-scale, in vivo-like tissue morphogenesis in 3D, improving insight into congenital disease phenotypes. Moreover, understanding the impact of boundary condition mechanics on kidney development benefits fundamental research and renal engineering.
    DOI:  https://doi.org/10.1038/s41467-025-63197-5
  12. Soft Matter. 2025 Aug 27.
    Cell mechanics, environmental geometry, and cell polarity control cell-cell collision outcomes.
    Yongtian Luo, Amrinder S Nain, Brian A Camley.
      Interactions between crawling cells, which are essential for many biological processes, can be quantified by measuring cell-cell collisions. Conventionally, experiments of cell-cell collisions are conducted on two-dimensional flat substrates, where colliding cells repolarize and move away upon contact with one another in "contact inhibition of locomotion" (CIL). Inspired by recent experiments that show cells on suspended nanofibers have qualitatively different CIL behaviors than those on flat substrates, we develop a phase field model of cell motility and two-cell collisions in fiber geometries. Our model includes cell-cell and cell-fiber adhesion, and a simple positive feedback mechanism of cell polarity. We focus on cell collisions on two parallel fibers, finding that larger cell deformability (lower membrane tension), larger positive feedback of polarization, and larger fiber spacing promote more occurrences of cells walking past one another. We can capture this behavior using a simple linear stability analysis on the cell-cell interface upon collision.
    DOI:  https://doi.org/10.1039/d5sm00359h
  13. Cell Rep. 2025 Aug 22. pii: S2211-1247(25)00947-7. [Epub ahead of print]44(9): 116176
    Matrix-induced nuclear remodeling and mechano-therapeutics.
    Jung-Hwan Lee, Yeo Gyun Yun, Hae-Won Kim.
      The extracellular matrix (ECM) provides structural support and mechanical cues that profoundly influence cellular behavior via nuclear mechanotransduction. This review discusses how ECM biophysical properties, including stiffness, topology, and spatial confinement, regulate nuclear mechanics and chromatin organization to determine cell fate across diverse pathophysiological contexts. We describe how mechanical signals propagate from the plasma membrane through cytoskeletal networks to modulate nuclear envelope tension, chromatin accessibility, and epigenetic landscapes. These matrix-driven nuclear changes orchestrate cellular responses in cancer progression, inflammation, fibrosis, stem cell differentiation, and age-related tissue dysfunction. Building on this mechanistic insight, we highlight emerging therapeutic strategies targeting the matrix-nucleus axis, such as tuning matrix properties to modulate chromatin accessibility, mechano-priming cells to enhance therapeutic outcomes, and targeting mechanosensitive molecules in the cytoskeletal-nuclear interface. Collectively, these approaches represent a promising paradigm leveraging mechanically induced epigenetic regulation and nuclear mechanobiology for disease treatment and tissue regeneration.
    Keywords:  CP: Cell biology
    DOI:  https://doi.org/10.1016/j.celrep.2025.116176
  14. RSC Adv. 2025 Aug 11. 15(35): 28452-28463
    Continuous pore size gradient enhances zonal-specific differentiation of stem cells in an osteochondral scaffold.
    Gioacchino Conoscenti, Kyra W Y Smith, Alessandro Pirosa, Francesco Carfì Pavia, Emily Y Zhang, Vincenzo La Carrubba, Valerio Brucato, Rocky S Tuan, Riccardo Gottardi.
      Cartilage and bone in articular joints are intimately linked within the osteochondral (OC) unit. Scaffold-based regenerative approaches in the joint often target both cartilage and the subchondral bone, taking advantage of the endogenous bone marrow stem cells made available by breaching the OC junction. However, the production of scaffolds for OC regeneration is challenging, as scaffolds must provide mechanical strength while also mimicking the local cartilage and bone microenvironments. To create an osteochondral scaffold, we used Thermally Induced Phase Separation (TIPS) that allows us to create a wide range of morphologies in terms of pore size and distribution by tuning thermal history. We created a poly-l-lactic acid (PLLA) scaffold with a continuous pore size gradient from 70 μm diameter on the cartilage repair side to over 200 μm diameter on the bone repair side. We hypothesized that the smaller pore size will support chondrogenesis while the larger pore size will induce an osteogenic phenotype. This hypothesis was confirmed using an innovative biphasic bioreactor capable of providing distinct and separate signaling cues for cartilage and bone differentiation, while allowing communication across the osteochondral junction, similar to the in vivo environment. Our findings suggested that the PLLA continuous pore-gradient structure may offer a clinically translatable solution to osteochondral defect repair by supporting zone-specific differentiation.
    DOI:  https://doi.org/10.1039/d5ra00540j
  15. Lab Chip. 2025 Aug 20.
    Accelerated maturation of branched organoids confined in collagen droplets.
    Iris Ruider, Anna Pastucha, Marion K Raich, Wentao Xu, Yan Liu, Maximilian Reichert, David Weitz, Andreas R Bausch.
      Droplet-based organoid culture offers several advantages over conventional bulk organoid culture, such as improved yield, reproducibility, and throughput. However, organoids grown in droplets typically display only a spherical geometry and lack the intricate structural complexity found in native tissue. By incorporating singularised pancreatic ductal adenocarcinoma cells into collagen droplets, we achieve the growth of branched structures, indicating a more complex interaction with the surrounding hydrogel. A comparison of organoid growth in droplets of different diameters showed that while geometrical confinement improves organoid homogeneity, it also impairs the formation of more complex organoid morphologies. Thus, only in 750 μm diameter collagen droplets did we achieve the consistent growth of highly branched structures with a morphology closely resembling the structural complexity achieved in traditional bulk organoid culture. Moreover, our analysis of organoid morphology and transcriptomic data suggests an accelerated maturation of organoids cultured in collagen droplets, highlighting a shift in developmental timing compared to traditional systems.
    DOI:  https://doi.org/10.1039/d5lc00287g
  16. Nat Commun. 2025 Aug 20. 16(1): 7438
    Tumor cell-adipocyte gap junctions activate lipolysis and contribute to breast tumorigenesis.
    Jeremy Williams, Roman Camarda, Serghei Malkov, Lisa J Zimmerman, Suzanne Manning, Dvir Aran, Andrew Beardsley, Daniel Van de Mark, Rachel Nakagawa, Yong Chen, Charles Berdan, Sharon M Louie, Celine Mahieu, Daphne Superville, Juliane Winkler, Elizabeth Willey, Erica J Hutchins, John D Gagnon, Seda Kilinc Avsaroglu, Kosaku Shinoda, Matthew Gruner, Hiroshi Nishida, K Mark Ansel, Zena Werb, Daniel K Nomura, Shingo Kajimura, Atul J Butte, Melinda E Sanders, Daniel C Liebler, Hope S Rugo, Gregor Krings, John A Shepherd, Andrei Goga.
      A pro-tumorigenic role for adipocytes has been identified in breast cancer, and reliance on fatty acid catabolism found in aggressive tumors. The molecular mechanisms by which tumor cells coopt neighboring adipocytes, however, remain incompletely understood. Here, we describe a direct interaction linking tumorigenesis to adjacent adipocytes. We examine breast tumors and their normal adjacent tissue from several patient cohorts, patient-derived xenografts, and mouse models, and find that lipolysis and lipolytic signaling are activated in neighboring adipose tissue. We find that functional gap junctions form between breast cancer cells and adipocytes. As a result, cAMP is transferred from breast cancer cells to adipocytes and activates lipolysis in a gap junction-dependent manner. We find that connexin 31 (GJB3) promotes receptor triple negative breast cancer growth and activation of lipolysis in vivo. Thus, direct tumor cell-adipocyte interaction contributes to tumorigenesis and may serve as a new therapeutic target in breast cancer.
    DOI:  https://doi.org/10.1038/s41467-025-62486-3
  17. iScience. 2025 Sep 19. 28(9): 113234
    Impact of 3D cell culture hydrogels derived from basement membrane extracts or nanofibrillar cellulose on CAR-T cell activation.
    Sonia Aristin Revilla, Alessandro Cutilli, Eugenia Cambiaso, Dedeke Rockx-Brouwer, Cynthia Lisanne Frederiks, Marc Falandt, Riccardo Levato, Onno Kranenburg, Caroline A Lindemans, Paul James Coffer, Victor Peperzak, Enric Mocholi, Marta Cuenca.
      Hydrogel-based 3D culture systems are increasingly used for preclinical evaluation of cell-based immunotherapies, including chimeric antigen receptor T (CAR-T) cells. However, hydrogel properties can influence T cell behavior, potentially affecting interpretation of immunotherapy studies. We assessed CD4+ T and CAR-T cell responses in two chemically undefined matrices-Matrigel and basement membrane extract (BME)- and in a synthetic nanofibrillar cellulose (NFC) hydrogel. Although NFC was mechanically stiffer, T cell activation and proliferation were higher in NFC than in Matrigel or BME. Murine CD4+ T cells acquired a regulatory phenotype in Matrigel and BME but not in NFC. Similarly, CAR-T cell function was reduced in Matrigel and BME but maintained in NFC. These findings underscore how matrix composition can shape T cell responses in 3D culture. NFC provides a chemically defined alternative that preserves T cell activity, supporting its use in more accurate preclinical testing of immunotherapies.
    Keywords:  Biological sciences; Biomaterials; Cell biology; Immune response; Materials science
    DOI:  https://doi.org/10.1016/j.isci.2025.113234
  18. Nat Commun. 2025 Aug 25. 16(1): 7922
    Soft porous metamaterials using inflation-induced buckling for smart actuation.
    Kieran Barvenik, Michael Bonthron, Anthony Jones, Eleonora Tubaldi.
      Cellular metamaterials represent unique platforms to manipulate structure-property relationships and enhance mechanical responses. While their unconventional behaviors have traditionally been obtained via pattern-transformations under compressive loading or deflation, we theoretically investigate and experimentally realize a new class of soft, porous metamaterials that undergo buckling instability upon inflation, unlocking superior programming and sequencing capabilities for soft intelligent machines. Our inflatable metamaterial reimagines the traditional rubber slab with periodic holes by incorporating a single internal pressure cavity. Upon inflation, the structure can be engineered to exhibit global short-wavelength buckling modes with a controllable circumferential lobe count of the cylindrical pores. First, we experimentally demonstrate the programmable post-buckling behavior by tuning the geometric parameters. Then, with a combination of analytical and numerical methods, we accurately predict the critical buckling pressure and pattern reconfiguration of the cellular metamaterial. By enabling different pattern rearrangements of the collapsing pores, we achieve a new actuation mechanism to suddenly reconfigure the global structure, selectively grasp slender objects, and operate multiple fluid channels with a single input.
    DOI:  https://doi.org/10.1038/s41467-025-63072-3
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