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Fibroblast polarization is a matrix-rigidity-dependent process controlled by focal adhesion mechanosensing
Masha Prager-Khoutorsky1, Alexandra Lichtenstein, Ramaswamy Krishnan
1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Nature Cell Biology
|November 15, 2011
Summary
Cell polarization and elongation depend on substrate rigidity. Focal adhesion orientation guides cell shape, with protein tyrosine kinases (PTKs) regulating these processes and mechanosensing.
Area of Science:
- Cell biology
- Biophysics
- Mechanobiology
Background:
- Cell elongation and polarization are fundamental morphogenetic responses.
- These processes are influenced by interactions with the extracellular matrix.
- Substrate rigidity plays a critical role in cell adhesion and behavior.
Purpose of the Study:
- To investigate the role of substrate rigidity in human fibroblast polarization.
- To determine the influence of focal adhesion formation and orientation on cell polarization.
- To explore the involvement of protein tyrosine kinases (PTKs) in regulating cell polarization and mechanosensing.
Main Methods:
- Culturing human fibroblasts on rigid and compliant substrates.
- Live-cell monitoring of cell behavior and focal adhesion dynamics.
- siRNA-mediated knockdown of 85 human protein tyrosine kinases (PTKs).
- Analysis of cell traction force generation and focal adhesion formation.
Main Results:
- Fibroblasts polarize on rigid substrates with large, oriented focal adhesions, but not on compliant substrates with small, radial adhesions.
- Focal adhesion alignment precedes cell elongation, suggesting it directs cell polarization.
- PTK knockdown altered cell polarization, traction force, and focal adhesion formation.
- Rigidity-dependent changes in mechanosensing correlated with cell polarization abnormalities.
Conclusions:
- Substrate rigidity critically influences fibroblast polarization via focal adhesion formation and orientation.
- Protein tyrosine kinases (PTKs) act as regulators of cell contractility and focal adhesion-mediated mechanosensing during polarization.
- PTK-dependent molecular checkpoints govern cell polarization stages by controlling contractility and mechanosensing.
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