bims-ecemfi Biomed News
on ECM and fibroblasts
Issue of 2026–05–10
eight papers selected by
Badri Narayanan Narasimhan, University of California, San Diego
  1. Matrix Viscoelasticity Regulates Dendritic Cell Migration and Immune Priming.
  2. Adaptive PEG Bis-dendron Hydrogels with Tunable Mechanics and Bioactivity.
  3. Active Microrheology Reveals Distinct ECM Mechanical Signatures Induced by Stromal Cells of Different Tissue Origins during Vascular Morphogenesis.
  4. Targeting the D93 cryptic collagen epitope alters integrin α2β1-dependent cellular migration and collagen remodeling in metastatic breast cancer.
  5. Breast cancer cell-derived extracellular vesicles accelerate collagen fibrillogenesis and integrate into the matrix.
  6. Uncovering Cancer-Associated Adipocytes: An Emerging Force Reshaping the Immunotherapy Landscape for Breast Cancer.
  7. MatriSpace: Identification and visualization of spatially resolved ECM gene expression patterns in health and disease.
  8. Predictability is dynamically constructed by topological collective modes in deterministic systems.
  1. Adv Mater. 2026 May 05. e23274
    Matrix Viscoelasticity Regulates Dendritic Cell Migration and Immune Priming.
    Wei-Hung Jung, Emie Humann, Joshua M Price, Yoav Binenbaum, Azra Haseki, Sanjana Iyer, David J Mooney.
      The tumor microenvironment shapes immune surveillance through its mechanical properties, yet the role of matrix viscoelasticity remains unclear. Here, we used a tunable collagen system that models human tissue viscoelasticity to define how matrix relaxation directs dendritic cell (DC) behavior. Slow-relaxing, elastic networks restrict actomyosin-driven remodeling, limiting DC motility and reducing DC-T cell encounters and activation. Blocking DC migration in fast-relaxing matrices recapitulated key aspects of the impaired T cell priming seen in elastic networks, identifying migration as a mechanical checkpoint for immune activation. Prolonged confinement in elastic matrices induced a mechanomemory state, locking DCs into a state of reduced motility and altered chromatin accessibility. Studies using patient-derived ependymoma samples confirmed these findings, establishing viscoelastic relaxation as a key physical regulator of immune priming. Together, this tunable viscoelastic platform provides a defined, human-relevant model to dissect and model mechanical control of immunity for therapeutic design.
    Keywords:  T cell priming; dendritic cell; mechanomemory; tumor microenvironment; viscoelastic extracellular matrix
    DOI:  https://doi.org/10.1002/adma.202523274
  2. Chem Mater. 2026 Apr 28. 38(8): 4319-4333
    Adaptive PEG Bis-dendron Hydrogels with Tunable Mechanics and Bioactivity.
    Evgeny Apartsin, Noël Richard, Birgit Habenstein, Antoine Loquet, Sophie Lecomte, Marie-Christine Durrieu.
      Most organoids are cultured in Matrigel, a complex and poorly defined matrix that limits our mechanistic understanding. Synthetic hydrogels offer a versatile alternative, providing precise control over mechanical and biochemical cues. Using two topologically different types of hydrogel precursors, branched poly-(ethylene glycol) (PEG) and PEG bisdendrons, we have obtained a library of hydrogels via thiol-ene cross-linking with branched PEG-thiol. Their chemical conversion was monitored by Raman spectroscopy, while swelling and mechanical properties, including elastic, viscoelastic, and relaxation parameters, were systematically evaluated. Bisdendron hydrogels dissipate stress through abundant weak interactions, conferring adaptive viscoelastic behavior, an underexplored feature in a 3D culture. To link macromolecular dynamics with bulk properties, polymer chain mobility and internal architecture were probed using MAS solid-state NMR and freeze-fracture cryo-SEM. To introduce bioactivity, RGD peptides were used and immobilized via thiol-ene chemistry, forming spatially organized clusters within the hydrogels. This strategy enables the design of customizable matrices with tunable mechanics, adjustable porosity, and controlled bioactive presentation, closely mimicking native microenvironments. Our platform can provide a chemically defined and versatile toolbox for organoid culturing.
    DOI:  https://doi.org/10.1021/acs.chemmater.6c00419
  3. ACS Biomater Sci Eng. 2026 May 04.
    Active Microrheology Reveals Distinct ECM Mechanical Signatures Induced by Stromal Cells of Different Tissue Origins during Vascular Morphogenesis.
    Michelle Lanterman, Irene W Zhang, Elliot L Botvinick, Andrew J Putnam.
      Stromal cells (SCs) provide important instructive cues for endothelial cells (ECs) during both normal and neoplastic vascularization. While the tissue-specific origins of ECs are important for function, the impact of SC identity on microvascular function and concurrent changes in tissue mechanical properties remains unclear. We previously showed robust microvasculature forms by codelivery of ECs and supportive SCs, and that SC identity regulates the rate of neovascularization and vessel functionality. Here, we used active microrheology (AMR) and traditional macrorheology to evaluate the dynamics of both local and global ECM mechanics in a 3D EC-SC co-culture model of vascular morphogenesis. Human umbilical vein ECs were co-embedded with either highly contractile lung fibroblasts (LFs) or significantly less contractile bone marrow-derived mesenchymal stromal cells (MSCs) within fibrin gels across various cell-seeding densities. By day 14, interconnected vascular networks developed, with rates of capillary morphogenesis higher in EC-LF than in EC-MSC co-cultures. Vascularization in EC-LF co-cultures was accompanied by ECM stiffening across length scales, in part due to cell contractility. AMR revealed highly heterogeneous local stiffness, with values ranging over 2 orders of magnitude in the same construct. AMR also identified the emergence of local stiffness anisotropy in the direction of capillary growth for EC-LF but not EC-MSC co-cultures by day 14, which was accompanied by significant matrix remodeling and local degradation. Together, these data suggest that different SC populations, through active cell contractility-dependent stiffening and matrix degradation, induce local mechanical cues that differentially influence vascular development. These results highlight the importance of the mechanobiological effects of SCs on the ECM in vascularized engineered tissues.
    Keywords:  endothelial cells; fibrin; microvasculature; optical tweezers microrheology; stiffness; stromal cells
    DOI:  https://doi.org/10.1021/acsbiomaterials.5c02134
  4. Sci Rep. 2026 May 06.
    Targeting the D93 cryptic collagen epitope alters integrin α2β1-dependent cellular migration and collagen remodeling in metastatic breast cancer.
    Jordan N Miner, Christopher L Emmerling, Joshua D Hamilton, Joseph Raite, Zoe Vittum, Peter C Brooks, Andre Khalil, Karissa Tilbury.
      Targeting the tumor-associated extracellular matrix (ECM) offers a promising strategy for breast cancer therapy. During cancer progression, collagen remodeling within the ECM exposes cryptic collagen epitope sites that antibodies can selectively recognize. Here, we investigate the therapeutic potential of targeting the D93 cryptic collagen epitope in 3D human metastatic breast cancer spheroids derived from MDA-MB-231 and MCF10CA1a (M4) cell lines embedded in collagen type I hydrogels. Treatment with monoclonal antibody (mAb) D93 reduced cellular migration into collagen type I hydrogels, an effect likely mediated by integrin α2β1. Two-photon microscopy further revealed that breast cancer cells drive the exposure of D93 sites and alter collagen architecture at both the fiber and fibril levels. Interestingly, collagen remodeling was altered more in the MDA-MB-231 spheroid models whereas the reduction in cellular migration was more pronounced in the M4 spheroid models, indicating a cell-line specific response to mAb D93. Together, these findings suggest that mAb D93 may inhibit integrin α2β1-dependent metastatic migration in breast cancer.
    Keywords:  Breast cancer; Collagen; Integrin; Migration; Second harmonic generation (SHG) microscopy; Spheroids
    DOI:  https://doi.org/10.1038/s41598-026-51149-y
  5. Mater Today Bio. 2026 Jun;38 103133
    Breast cancer cell-derived extracellular vesicles accelerate collagen fibrillogenesis and integrate into the matrix.
    Nicky W Tam, Rumiana Dimova, Amaia Cipitria.
      Though extracellular vesicles (EVs) contain much of the cellular machinery required for actively remodeling extracellular matrix (ECM), they are mostly appreciated for their roles in reprogramming cell proxies. Using a bottom-up biomimetic system, we show that breast cancer cell-derived EVs at the nanoscale can play an active role in collagen I matrix formation at the microscale. EVs nucleate new fibrils, recruiting collagen molecules from solution and enhancing fibril growth and network formation, resulting in more densely packed matrices with significantly increased storage and loss moduli. These effects are specific to EV membrane composition and cannot be reproduced using trypsinized EVs, synthetic liposomes, or mechanically extruded plasma membrane material. EVs become integrated into the fibril structures that they help form, reminiscent of matrix vesicles found within tissues. This represents a plausible way by which EVs are deposited into the ECM, becoming signaling cues for resident cells.
    Keywords:  Bottom-up synthetic biology; Cancer; Extracellular matrix; Extracellular vesicles; Soft matter mechanics
    DOI:  https://doi.org/10.1016/j.mtbio.2026.103133
  6. Curr Med Chem. 2026 Apr 29.
    Uncovering Cancer-Associated Adipocytes: An Emerging Force Reshaping the Immunotherapy Landscape for Breast Cancer.
    Ke Qian, Shujun Xu, Ke Zhang, Hongyan Zhang.
      The progression of breast cancer is intricately linked to the dynamic crosstalk between tumor cells and stromal cells. Within this complex interplay, Cancer-Associated Adipocytes (CAAs) have emerged as pivotal stromal components driving breast cancer malignancy by establishing a unique "adipose-immune" interface-one that integrates adipose-derived metabolic cues with immune cell dynamics to create a niche that accelerates tumor invasion, angiogenesis, and treatment resistance. This review systematically analyzes the roles of CAAs in breast cancer pathogenesis, focusing on how CAAs regulate the Tumor Immune Microenvironment (TIME) and the Adipose Tissue Microenvironment (ATME) individually and how they influence therapeutic responses through their interplay. A particular emphasis is placed on the functional heterogeneity of CAAs across different breast cancer subtypes and metabolic contexts, and its implications for shaping immunosuppressive niches and immunotherapy resistance. Specific mechanisms include: reshaping adipokine and inflammatory cytokine profiles to foster a pro-tumorigenic secretory landscape; inducing metabolic reprogramming in tumor cells to sustain aggressive growth; mediating intercellular signaling via exosomes to propagate malignant traits; altering immune cell functional states to shift toward an immunosuppressive phenotype; and promoting the establishment of immune escape pathways. Based on these mechanisms, the review synthesizes CAA-targeted therapeutic strategies for breast cancer, including: disrupting key adipokine-mediated signaling cascades to interrupt tumor-stroma communication, modulating CAA-secreted factors to reorient immune cell activities toward anti-tumor functions, and rewiring lipid metabolic pathways in the TIME to enhance therapeutic sensitivity. In-depth dissection of CAA functional networks is crucial for elucidating their pathogenic significance in breast cancer and fueling precision immunotherapy innovation, as such insights may open avenues for rebalancing TIME immune interactions and boosting immunotherapeutic efficacy.
    Keywords:  Breast cancer; adipose tissue microenvironment; cancer-associated adipocytes; immunotherapy; stromal cells.; tumor immune microenvironment
    DOI:  https://doi.org/10.2174/0109298673424411251204102903
  7. bioRxiv. 2026 Apr 29. pii: 2026.04.26.720198. [Epub ahead of print]
    MatriSpace: Identification and visualization of spatially resolved ECM gene expression patterns in health and disease.
    Ayomide Oshinjo, Daiqing Chen, Petar Petrov, Valerio Izzi, Alexandra Naba.
      The extracellular matrix (ECM) is a highly dynamic network of proteins forming the structural organizer of all tissues. Different cell populations contribute to the assembly of the 150+ proteins of a functional ECM. In addition, different ECM subtypes, supporting distinct cellular functions, are found in every organ. Spatial transcriptomics (ST) provides a unique, yet untapped, opportunity to identify which cell populations contribute to ECM production with spatial context. Applied to healthy and diseased samples, this method can identify ECM changes that could be exploited for therapeutic purposes. Here, we introduce MatriSpace, a computational framework to mine ST datasets with a focus on ECM genes. MatriSpace offers two operating modes: researchers can either upload their own ST datasets or explore a large collection of public datasets. Upon analysis, MatriSpace returns spatially resolved maps of matrisome gene expression in relation to cell populations, at multiple levels: from single-gene analysis to tissue niches and functional ECM units. MatriSpace is available as an R package and an online Shiny App (https://matrinet.shinyapps.io/matrispace), making it accessible to all users regardless of their level of expertise.
    DOI:  https://doi.org/10.64898/2026.04.26.720198
  8. ArXiv. 2026 Apr 01. pii: arXiv:2604.01088v1. [Epub ahead of print]
    Predictability is dynamically constructed by topological collective modes in deterministic systems.
    Lars Koopmans, Elinor M Kay, Hyun Youk.
      Deterministic many-body systems governed by simple interactions can self-organize into macroscopic patterns, and the determinants of long-time behavior are assumed to be encoded in the initial configuration. Here we show that predictability can instead be constructed dynamically rather than being accessible in the initial configuration. We study a generalized cellular automaton of secrete-and-sense cells that self-organizes from disorder into static configurations, rectilinear waves, or spiral waves. Although dynamics are deterministic, the final outcome cannot be reliably inferred from the initial state alone. Treating cell states as a discrete phase field, we uncover emergent topological modes - charged vortices connected by strings that form non-contractible loops. Tracking their dynamics reveals that predictive signatures of macroscopic fate appear only late in the trajectory: vortex annihilation becomes readable through loop loss, whereas vortex persistence remains unreadable until spiral waves form abruptly. These results show how predictability can be dynamically constructed in deterministic nonequilibrium systems.
This page is being maintained by Thomas Krichel. It was last updated on 2026‒05‒11 at 13:59.