bims-ecemfi Biomed News
on ECM and fibroblasts
Issue of 2025–02–16
two papers selected by
Badri Narayanan Narasimhan, University of California, San Diego
  1. Epithelial Cell Mechanoresponse to Matrix Viscoelasticity and Confinement Within Micropatterned Viscoelastic Hydrogels.
  2. Effects of Cell Seeding Density, Extracellular Matrix Composition, and Geometry on Yes-Associated Protein Translocation in Corneal Fibroblasts.
  1. Adv Sci (Weinh). 2025 Feb 14. e2408635
    Epithelial Cell Mechanoresponse to Matrix Viscoelasticity and Confinement Within Micropatterned Viscoelastic Hydrogels.
    Giuseppe Ciccone, Mariana Azevedo Gonzalez-Oliva, Marie Versaevel, Marco Cantini, Massimo Vassalli, Manuel Salmeron-Sanchez, Sylvain Gabriele.
      Extracellular matrix (ECM) viscoelasticity has emerged as a potent regulator of physiological and pathological processes, including cancer progression. Spatial confinement within the ECM is also known to influence cell behavior in these contexts. However, the interplay between matrix viscoelasticity and spatial confinement in driving epithelial cell mechanotransduction is not well understood, as it relies on experiments employing purely elastic hydrogels. This work presents an innovative approach to fabricate and micropattern viscoelastic polyacrylamide hydrogels with independently tuneable Young's modulus and stress relaxation, specifically designed to mimic the mechanical properties observed during breast tumor progression, transitioning from a soft dissipative tissue to a stiff elastic one. Using this platform, this work demonstrates that matrix viscoelasticity differentially modulates breast epithelial cell spreading, adhesion, YAP nuclear import and cell migration, depending on the initial stiffness of the matrix. Furthermore, by imposing spatial confinement through micropatterning, this work demonstrates that confinement alters cellular responses to viscoelasticity, including cell spreading, mechanotransduction and migration. These findings establish ECM viscoelasticity as a key regulator of epithelial cell mechanoresponse and highlight the critical role of spatial confinement in soft, dissipative ECMs, which was a previously unexplored aspect.
    Keywords:  confinement; epithelial cells; extracellular matrix; hydrogels; micropatterning; viscoelasticity
    DOI:  https://doi.org/10.1002/advs.202408635
  2. Int J Mol Sci. 2025 Jan 29. pii: 1183. [Epub ahead of print]26(3):
    Effects of Cell Seeding Density, Extracellular Matrix Composition, and Geometry on Yes-Associated Protein Translocation in Corneal Fibroblasts.
    Divya Subramanian, Nathaniel S Tjahjono, Satweka Nammi, Miguel Miron-Mendoza, Victor D Varner, W Matthew Petroll, David W Schmidtke.
      Corneal fibroblasts are central to normal and abnormal wound healing in the cornea. During the wound healing process, several biochemical and biophysical signals that are present in the extracellular matrix (ECM) play critical roles in regulating corneal fibroblast behavior. The translocation and activation of Yes-associated protein (YAP)-a main transcriptional factor in the Hippo signaling pathway-is one example of mechanotransduction involving these signals. However, how corneal fibroblasts integrate these simultaneous cues is unknown. In this study, we utilized well-defined micropatterns of aligned collagen fibrils and other ECM proteins to explore the effects of cell density, topography, geometric confinement, and ECM composition on the translocation of YAP in corneal fibroblasts. We observed that when human corneal fibroblasts (HTKs) were confined to narrow micropatterns (50 μm and 100 μm) of proteins, there was a high degree of cell alignment irrespective of cell seeding density. However, the location of YAP was dependent upon the cell seeding density, ECM composition, and topography. YAP was more nuclear-localized on substrates coated with aligned collagen fibrils or fibronectin as compared to substrates coated with monomeric collagen, random collagen fibrils, or poly-L-Lysine. In addition, we also observed that YAP nuclear localization was significantly reduced when HTKs were cultured on aligned collagen fibrils, monomeric collagen, or fibronectin in the presence of monoclonal blocking antibodies against α5 or β1 integrin subunits. Finally, we observed that HTK cells formed fibrillar fibronectin on both monomeric collagen and aligned collagen fibrils. These findings provide new insights into how simultaneous biochemical and biophysical cues affect YAP localization in corneal fibroblasts.
    Keywords:  YAP; collagen fibrils; confinement; cornea; corneal fibroblasts; micropatterns; topography
    DOI:  https://doi.org/10.3390/ijms26031183
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