bims-ecemfi Biomed News
on ECM and fibroblasts
Issue of 2025–05–25
two papers selected by
Badri Narayanan Narasimhan, University of California, San Diego
  1. Matrix stiffness and viscoelasticity influence human mesenchymal stem cell immunomodulation.
  2. A direct computational assessment of vinculin-actin unbinding kinetics reveals catch-bonding behavior.
  1. Mechanobiol Med. 2025 Mar;3(1): 100111
    Matrix stiffness and viscoelasticity influence human mesenchymal stem cell immunomodulation.
    Sara J Olsen, Rose E Leader, Abigail L Mortimer, Bethany Almeida.
      Human mesenchymal stem cells (hMSCs) have immense wound healing potential due to their immunomodulatory behavior. To control this behavior and reduce heterogeneity, researchers look to biomaterials, as matrix stiffness and viscoelasticity have been shown to control hMSC immunomodulation. However, the understanding of the effects of these biophysical cues on hMSC immunomodulation remains limited; a broad study investigating the potentially synergistic effects of matrix stiffness and viscoelasticity on hMSC immunomodulation is needed in order to support future work developing biomaterials for hMSC wound healing applications. We developed polyacrylamide (PAAm) gels with varying matrix stiffnesses with or without a viscoelastic element and explored the effects of these on hMSC-matrix interactions and immunomodulatory cytokine expression in both a normal growth media and an immunomodulatory growth media mimetic of a chronic, non-healing wound. Expression of IL-10, VEGF, and PGE2 were upregulated in immunomodulatory growth media over normal growth media, demonstrating the synergistic effects of biochemical signaling on hMSC immunomodulatory behavior. In addition, the addition of a viscoelastic element had both inhibitory and accentuating effects based on the cytokine and biochemical signaling in the cell culture media. Overall, this study provides a broad perspective on the immunomodulatory behavior of hMSCs due to stiffness and viscoelasticity.
    Keywords:  Biomaterials; Human mesenchymal stem cell; Immunomodulation; Matrix stiffness; Matrix viscoelasticity
    DOI:  https://doi.org/10.1016/j.mbm.2024.100111
  2. Proc Natl Acad Sci U S A. 2025 May 27. 122(21): e2425982122
    A direct computational assessment of vinculin-actin unbinding kinetics reveals catch-bonding behavior.
    Willmor J Peña Ccoa, Fatemah Mukadum, Aubin Ramon, Guillaume Stirnemann, Glen M Hocky.
      Vinculin forms a catch bond with the cytoskeletal polymer actin, displaying an increased bond lifetime upon force application. Notably, this behavior depends on the direction of the applied force, which has significant implications for cellular mechanotransduction. In this work, we present a comprehensive molecular dynamics simulation study, employing enhanced sampling techniques to investigate the thermodynamic, kinetic, and mechanistic aspects of this phenomenon at physiologically relevant forces. We dissect a catch bond mechanism in which force shifts vinculin between either a weakly or strongly bound state. Our results demonstrate that models for these states have unbinding times consistent with those from single-molecule studies, and suggest that both have some intrinsic catch-bonding behavior. We provide atomistic insight into this behavior, and show how a directional pulling force can promote the strong or weak state. Crucially, our strategy can be extended to measure the difficult-to-capture effects of small mechanical forces on biomolecular systems in general, and those involved in mechanotransduction more specifically.
    Keywords:  actin; catch bond; molecular dynamics; rate constants; vinculin
    DOI:  https://doi.org/10.1073/pnas.2425982122
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