Contractile myosin rings and cofilin-mediated actin disassembly orchestrate ECM nanotopography sensing
| Autor: | John T. Connelly, Stefania Di Cio, Thomas Iskratsch, Julien E. Gautrot |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Biophysics
Focal adhesion assembly Bioengineering macromolecular substances 02 engineering and technology Myosins Biomaterials Focal adhesion 03 medical and health sciences Myosin Cell Adhesion Nanotopography Actin 030304 developmental biology 0303 health sciences Focal Adhesions biology Chemistry Vinculin Cofilin 021001 nanoscience & nanotechnology Actin cytoskeleton Actins Cell biology Extracellular Matrix Actin Cytoskeleton Actin Depolymerizing Factors Mechanics of Materials Ceramics and Composites biology.protein 0210 nano-technology |
| Zdroj: | Biomaterials |
| ISSN: | 1878-5905 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect