Contractile myosin rings and cofilin-mediated actin disassembly orchestrate ECM nanotopography sensing.

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  • Additional Information
    • Source:
      Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 8100316 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-5905 (Electronic) Linking ISSN: 01429612 NLM ISO Abbreviation: Biomaterials Subsets: MEDLINE
    • Publication Information:
      Publication: <1995-> : Amsterdam : Elsevier Science
      Original Publication: [Guilford, England] : IPC Science and Technology Press, 1980-
    • Subject Terms:
      Actin Depolymerizing Factors* ; Actins* ; Cell Adhesion* ; Extracellular Matrix*; Actin Cytoskeleton ; Focal Adhesions ; Myosins
    • Abstract:
      The nanotopography and nanoscale geometry of the extra-cellular matrix (ECM) are important regulators of cell adhesion, motility and fate decision. However, unlike the sensing of matrix mechanics and ECM density, the molecular processes regulating the direct sensing of the ECM nanotopography and nanoscale geometry are not well understood. Here, we use nanotopographical patterns generated via electrospun nanofibre lithography (ENL) to investigate the mechanisms of nanotopography sensing by cells. We observe the dysregulation of actin dynamics, resulting in the surprising formation of actin foci. This alteration of actin organisation is regulated by myosin contractility but independent of adapter proteins such as vinculin. This process is highly dependent on differential integrin expression as β3 integrin expressing cells, more sensitive to nanopattern dimensions than β1 integrin expressing cells, also display increased perturbation of actin assembly and actin foci formation. We propose that, in β3 integrin expressing cells, contractility results in the destabilisation of nanopatterned actin networks, collapsing into foci and sequestering regulators of actin dynamics such as cofilin that orchestrate disassembly. Therefore, in contrast to the sensing of substrate mechanics and ECM ligand density, which are directly orchestrated by focal adhesion assembly, we propose that nanotopography sensing is regulated by a long-range sensing mechanism, remote from focal adhesions and mediated by the actin architecture.
      (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)
    • Grant Information:
      FS/14/30/30917 United Kingdom BHF_ British Heart Foundation; PG/20/6/34835 United Kingdom BHF_ British Heart Foundation
    • Contributed Indexing:
      Keywords: Actin cytoskeleton; Cofilin; Nanofibres; Nanopatterning
    • Accession Number:
      0 (Actin Depolymerizing Factors)
      0 (Actins)
      EC 3.6.4.1 (Myosins)
    • Publication Date:
      Date Created: 20200114 Date Completed: 20210430 Latest Revision: 20230301
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.biomaterials.2019.119683
    • Accession Number:
      31927180