bims-ecemfi Biomed News
on ECM and fibroblasts
Issue of 2026–01–04
nine papers selected by
Badri Narayanan Narasimhan, University of California, San Diego
  1. Stabilization of adhesions controls F-actin architecture in mechanotransduction.
  2. Adaptive Cytoskeletal Responses to Extracellular Environment Viscosity Modulate Cell Migration.
  3. Leveraging Viscosity to Unlock the Osteogenic Potential of BMP-2 Mimetic DWIVA.
  4. Atypical E-cadherin attachments mediate melanoblast migration through confined epithelial spaces.
  5. Guidance for 3D traction force microscopy today and in the next decade.
  6. Neuronal heterogeneity of normalization strength in a circuit model.
  7. Trade-off between branching and polarity controls decision-making during cell migration.
  8. Spatially distinct cellular and molecular landscapes define prognosis in triple-negative breast cancer.
  9. Tunable Wrinkled Topographies Direct Dendritic Cell Maturation and Immune Phenotypes.
  1. Commun Mater. 2025 ;6(1): 288
    Stabilization of adhesions controls F-actin architecture in mechanotransduction.
    Keith R Carney, Remi Sondaz, Wesley Sturgess, Kabilan Sakthivel, Jungkyu Kim, Vinay Swaminathan, Tamara C Bidone.
      A cell's ability to sense and respond to the mechanical properties of the extracellular matrix (ECM) is essential for maintaining tissue homeostasis, and its disruption contributes to diseases such as fibrosis, cardiovascular disorders, and cancer. Effective mechanical coupling between the plasma membrane, the underlying filamentous actin (F-actin) cytoskeleton, and integrin-based adhesion complexes (IACs) is required to link ECM mechanics to cell morphology, yet the underlying mechanisms remain incompletely understood. Here, we combine computational modeling and high-resolution imaging to show that integrin-ECM bonds determine F-actin cytoskeleton organization. On soft substrates, short-lived IACs bonds allow rapid actin retrograde flow and dense branching, restricting protrusion and limiting cell spreading. In contrast, stiff substrates or Mn²⁺-mediated integrin activation stabilize adhesions, promote filament alignment, and drive membrane protrusion for cell spreading. These cytoskeletal transitions arise from feedback between adhesion strength and the spatial positioning of the F-actin barbed ends relative to the leading-edge membrane. This positioning determines whether filaments polymerize into linear bundles or branch into dendritic networks, each generating distinct protrusive forces that regulate cell spreading. Collectively, our findings establish integrin-ECM bond stability as a key regulator of F-actin cytoskeleton organization and cell morphology.
    Keywords:  Computational biophysics; Soft materials
    DOI:  https://doi.org/10.1038/s43246-025-01006-8
  2. ACS Nano. 2025 Dec 30.
    Adaptive Cytoskeletal Responses to Extracellular Environment Viscosity Modulate Cell Migration.
    Zhongya Lin, Xindong Chen, Xi-Qiao Feng.
      Cell migration is a pivotal process in metastasis, allowing cancer cells to invade surrounding tissues and disseminate to distant organs. While extracellular environment (ECE) viscosity serves as a critical modulator of cell motility, its regulatory mechanisms remain unclear. This study presents a mechanobiological model to investigate how ECE viscosity modulates cancer cell migration by regulating some key processes, including actin polymerization, retrograde flow, and adhesion adaptations. Our results reveal a biphasic response: a moderate increase in ECE viscosity enhances actin filament network density and adhesion strength, thereby accelerating migration, whereas excessively high viscosity hinders movement due to too large mechanical resistance. Furthermore, we identify a short-term migration memory phenomenon where cancer cells exposed to high-viscosity environments retain elevated migration speeds after transitioning to low-viscosity conditions. This memory effect is sustained by the continued assembly of cytoskeletal proteins, such as actin monomers and Arp2/3. These analyses reveal an adaptive mechano-chemo-biological mechanism by which cancer cells integrate and respond to mechanical cues from their viscous environment to optimize migration and advance the understanding of cancer cell migration in various tissue environments.
    Keywords:  actin dynamics; cell migration; mechanobiology; memory mechanism; viscosity
    DOI:  https://doi.org/10.1021/acsnano.5c11355
  3. Small. 2025 Dec 30. e08366
    Leveraging Viscosity to Unlock the Osteogenic Potential of BMP-2 Mimetic DWIVA.
    Finlay Cunniffe, Ziyuan Luo, Eva Barcelona-Estaje, Eva Forrest, Manuel Salmeron-Sanchez, Marco Cantini.
      Growth factor mimetics offer great potential for osteogenic biomaterials; yet, their use remains limited, likely due to an incomplete understanding of the effects of the microenvironment on their activity. The extracellular matrices (ECMs) where growth factors are presented in vivo are viscoelastic environments, where dynamic receptor-ligand interactions drive cellular responses. Here, supported lipid bilayers of varying viscosity are used as 2D dynamic ECM models, where the bone morphogenetic 2 (BMP-2) mimetic DWIVA is presented to mesenchymal stem cells alongside the adhesive peptide RGD. DWIVA is demonstrated to have no impact on mechanotransductive processes, including actin organisation, focal adhesion formation and YAP localisation, which are exclusively controlled by viscosity via RGD. Interestingly, DWIVA promotes osteogenic markers' expression only on a viscous bilayer, through a process that involves non-canonical BMP-2 pathways; on a mobile bilayer or on a static control, it lacks osteogenic activity. Crucially, osteogenesis is accompanied by a translocation of BMP receptor 1a to the cell edge, where it colocalises with focal adhesions. Our ECM models hence reveal that both a viscosity-enabled threshold of cell-generated forces and a dynamic environment are necessary to harness the osteogenic potential of DWIVA, uncovering key microenvironment properties for the design of DWIVA-based biomaterials.
    Keywords:  BMP‐2; DWIVA; mesenchymal stem cell; osteogenesis; viscosity
    DOI:  https://doi.org/10.1002/smll.202508366
  4. J Cell Biol. 2026 Mar 02. pii: e202508144. [Epub ahead of print]225(3):
    Atypical E-cadherin attachments mediate melanoblast migration through confined epithelial spaces.
    Denay J K Richards, Brandon M Trejo, Parijat Sil, Abhishek Biswas, Rebecca A Jones, Lionel Larue, Danelle Devenport.
      Epithelial tissues are populated with accessory cells including pigment-producing melanocytes, which must migrate between tightly adherent epithelial cells, but how cells migrate through confined epithelial spaces without impairing barrier function is poorly understood. Using live imaging of the mouse epidermis, we captured the migration of embryonic melanocytes (melanoblasts) while simultaneously visualizing the basement membrane or epithelial surfaces. We show that melanoblasts migrate through basal and suprabasal layers of the epidermis where they use keratinocyte surfaces, as well as the basement membrane, as substrates for migration. Melanoblasts form atypical and dynamic E-cadherin attachments to keratinocytes that largely lack cytoplasmic catenins known to anchor E-cadherin to F-actin. We show E-cadherin is needed in both melanoblasts and keratinocytes to stabilize migratory protrusions, and that depleting E-cadherin results in reduced melanoblast motility and ventral depigmentation in adult mice. These findings illustrate how migratory cells modify the cell adhesion machinery to invade between connected epithelial cells without interrupting the skin barrier.
    DOI:  https://doi.org/10.1083/jcb.202508144
  5. Nat Methods. 2025 Dec 29.
    Guidance for 3D traction force microscopy today and in the next decade.
    Jorge Barrasa-Fano, Apeksha Shapeti, Alejandro Apolinar-Fernández, Laurens Kimps, Bart Smeets, José Antonio Sanz-Herrera, Hans Van Oosterwyck.
      The field of mechanobiology studies how mechanical forces influence cell behavior, relying on tools like traction force microscopy (TFM) to quantify cell forces exerted on the extracellular matrix. While well established for two-dimensional in vitro systems, its three-dimensional form, 3DTFM, remains underutilized despite notable technical advancements. Here, we outline common skepticism about 3DTFM, detailing current experimental and computational strategies to address its limitations. We describe how to integrate 3DTFM with biological readouts, focusing on its application in long-term experiments. We discuss metrics for data interpretation and how pairing these with optimal traction recovery methods can address specific biological questions. Finally, we outline future directions by proposing combinations with emerging technologies to address challenges like extracellular matrix heterogeneity and intracellular stress analysis within three-dimensional cell clusters. By addressing these critical gaps, this Perspective aims to advance 3DTFM's utility, promote its broader adoption and guide future developments in mechanobiology.
    DOI:  https://doi.org/10.1038/s41592-025-02934-6
  6. Sci Adv. 2026 Jan 02. 12(1): eadv9396
    Neuronal heterogeneity of normalization strength in a circuit model.
    Deying Song, Douglas Ruff, Marlene Cohen, Chengcheng Huang.
      Neurons in higher-order visual areas integrate information through a canonical computation called normalization. The strength of normalization is highly heterogeneous across neurons, and this heterogeneity correlates with attention-mediated modulations in neural responses. However, the circuit mechanism underlying the heterogeneous normalization strength is unclear. In this work, we study normalization in a spiking neuron network model of visual cortex. Our model reveals that the heterogeneity of normalization strength is highly correlated with the inhibitory current each neuron receives. The correlation between inhibition and other synaptic inputs explains the experimentally observed dependence of spike count correlations on normalization strength. Further, we find that neurons with stronger normalization encode information more efficiently, and that networks with more heterogeneity in normalization encode visual stimuli with higher information and capacity. Together, our model provides a mechanistic explanation of heterogeneous normalization strengths in the visual cortex and sheds light on the computational benefits of neuronal heterogeneity.
    DOI:  https://doi.org/10.1126/sciadv.adv9396
  7. Sci Adv. 2026 Jan 02. 12(1): eads2734
    Trade-off between branching and polarity controls decision-making during cell migration.
    Jiayi Liu, Javier Boix-Campos, Jonathan E Ron, Johan M Kux, Magdalena E M Oremek, Adriano G Rossi, Nir S Gov, Pablo J Sáez.
      Motile cells often face microenvironmental constraints and obstacles that force them to extend multiple protrusions. However, the analysis of shape dynamics during directional decision-making has been restricted to single junctions. Here, we combined live-cell imaging and a coarse-grained model to study the migratory behavior of highly branched cells while simultaneously facing several junctions. The theoretical model predicts that the choice of a new direction is determined by the competition between the cellular protrusions in the form of seesaw oscillations. We found that macrophages and endothelial cells display different regimes moving on hexagonal networks, despite sharing a mesenchymal (i.e., adhesion-dependent) migratory strategy. The model describes the motility of both cell types and reveals a trade-off between branching and speed: Having many protrusions allows local microenvironmental exploration for directional cues, but long-range migration efficiency improves with fewer protrusions. Collectively, our data highlight the relevance and provide insights for the regulation of shape dynamics during cell navigation in complex geometries.
    DOI:  https://doi.org/10.1126/sciadv.ads2734
  8. Cell Rep. 2025 Dec 31. pii: S2211-1247(25)01524-4. [Epub ahead of print]45(1): 116752
    Spatially distinct cellular and molecular landscapes define prognosis in triple-negative breast cancer.
    Kavitha Mukund, Darya Veraksa, David Frankhouser, Lixin Yang, Jerneja Tomsic, Raju Pillai, Srijan Atti, Zahra Mesrizadeh, Daniel Schmolze, Jovanny Zabaleta, Xiao-Cheng Wu, Mary-Anne LeBlanc, Lucio Miele, Augusto Ochoa, Victoria Seewaldt, Shankar Subramaniam.
      Triple-negative breast cancer (TNBC) is a prevalent breast cancer subtype with the lowest 5-year survival. Several factors influence outcomes, but their inherent molecular and cellular heterogeneity are increasingly acknowledged as crucial determinants. Here, we report on the spatio-molecular heterogeneity underlying TNBC tumors in a retrospective, treatment-naive cohort with differential prognoses (17 good prognoses [GPx] >15-year survival and 15 poor prognoses [PPx] <3-year survival]) profiled using GeoMx Digital Spatial Profiler. Analyses reveal that epithelial and microenvironment (TME) states are transcriptionally distinct between groups. Invasive GPx epithelia show an increase in immune transcripts, with a more immune-rich TME (via IF). PPx epithelia, in contrast, are more metabolically and translationally active, with a mesenchymal/fibrotic TME. Pre-cancerous epithelia in PPx exhibit a presence of aggressiveness, marked by increased EMT signaling and complement activity. We identify distinct epithelial gene signatures for PPx and GPx that can accurately classify diagnostic samples and likely inform therapy.
    Keywords:  C3 complement; CP: cancer; GeoMx DSP; TNBC; epithelia; immune mimicry; impressionable epithelium; pre-cancerous; prognosis; triple-negative breast cancer; tumor microenvironment
    DOI:  https://doi.org/10.1016/j.celrep.2025.116752
  9. Acta Biomater. 2025 Dec 30. pii: S1742-7061(25)00957-2. [Epub ahead of print]
    Tunable Wrinkled Topographies Direct Dendritic Cell Maturation and Immune Phenotypes.
    Ajay Chavda, Xingwu Zhou, Mohammad Asadi Tokmedash, James J Moon, Jouha Min.
      Dendritic cells (DCs) are potent regulators of immunity with therapeutic potential in cancer, autoimmune disorders, and implant tolerance. However, clinical translation is limited by poor scalability, limited survival/retention after delivery, and difficulty controlling DC immune responses. Biomaterials have been explored to address these challenges, but the role of surface topography in DC regulation remains poorly understood. Here, we used a custom bottom-up nanofabrication method to create wrinkled multilayer coatings with precisely tunable nano-, submicro-, and microscale topographies. Using this platform, we systematically investigated the impact of topographical cues on DC behavior, using the DC2.4 cell line and primary bone marrow-derived DCs (BMDCs) as biological models. We found that distinct topographies drive DCs toward divergent phenotypes. Microscale wrinkles promoted an immunogenic mature state, with elevated pro-inflammatory cytokines (IL-6, IL-12, and TNF-α), high co-stimulation and NF-κB activation, and strong T-cell activation potential. Submicro-scale patterns induced an intermediate mature state with homeostatic and tolerogenic potential. Submicro exhibited increased TGF-β and IL-10, reduced cross-presentation, and weak T-cell activation in the DC2.4 cell line. However, BMDCs expressed intermediate maturation marker levels and NF-κB activation without increased cytokine secretion. In contrast, nanoscale wrinkles and planar controls preserved DC immaturity with high antigen uptake and low maturation, though planar surfaces showed poor adhesion, limiting their utility for delivery or ex vivo culture. These findings identify surface topography as a key regulator of DC immune programming. Our versatile, scalable fabrication strategy provides a broadly applicable platform for probing immune cell-material interactions and advancing biomaterials for DC-based immunotherapies and related applications. STATEMENT OF SIGNIFICANCE: Immune therapies increasingly rely on dendritic cells (DCs), yet current biomaterials mainly use biochemical signals to guide their behavior. This study introduces a new approach using precisely engineered surface topographies to influence DC function through physical cues alone. By creating tunable wrinkled MXene coatings, we show for the first time that different topographical scales can maintain DC immaturity or induce maturation with either homeostatic or immunogenic polarization potential. Unlike prior studies that focus on general surface roughness or chemistry, we demonstrate a topography-specific effect validated in both cell line and primary DCs. This work establishes surface architecture as a powerful design parameter for immune-instructive biomaterials, with potential to improve vaccine development and cell-based immunotherapies.
    Keywords:  Biomaterials; Dendritic Cells; Immunomodulation; Surface Topography; Wrinkled Surfaces
    DOI:  https://doi.org/10.1016/j.actbio.2025.12.050
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