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Stimulation of integrin-mediated cell contractility by fibronectin polymerization.
D C Hocking1, J Sottile, K J Langenbach
1Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York 14642, USA. denise_hocking@urmc.rochester.edu
The Journal of Biological Chemistry
|April 1, 2000
Summary
Fibronectin polymerization stimulates cell contractility and spreading in collagen gels via a Rho-dependent mechanism. This process is critical for generating cytoskeletal tension and regulating cell functions during matrix remodeling.
Area of Science:
- Cell Biology
- Biochemistry
- Biophysics
Background:
- Integrin ligation to extracellular matrix (ECM) molecules links the matrix to the cytoskeleton.
- ECM deposition and remodeling during wound healing and development can influence cell functions through mechanical forces.
- Tensile forces modulate integrin-mediated cell migration and proliferation.
Purpose of the Study:
- To investigate the effect of fibronectin polymerization on mechanical tension generation by cells.
- To determine how fibronectin polymerization influences cell spreading and contractility.
- To elucidate the molecular mechanisms underlying fibronectin-mediated cell contractility.
Main Methods:
- Utilizing the ability of cells to contract floating collagen gels.
- Assessing cell spreading and contractility in response to fibronectin polymerization.
- Investigating the role of Rho signaling and integrin ligation in fibronectin-stimulated contractility.
- Employing fibronectin fragments, RGD peptides, and polymerization inhibitors.
Main Results:
- Fibronectin polymerization promotes cell spreading and stimulates Rho-dependent cell contractility in collagen gels.
- Integrin ligation is necessary but not sufficient; fibronectin fragments alone do not induce tension or spreading.
- Polyvalent RGD peptides and pre-polymerized fibronectin do not stimulate contractility.
- Inhibitors of fibronectin polymerization block fibronectin-induced contractility, highlighting polymerization's critical role.
Conclusions:
- Fibronectin polymerization is a critical trigger for cytoskeletal tension generation.
- Rho-mediated cell contractility is regulated by fibronectin polymerization.
- This study suggests a novel mechanism for how ECM fibronectin regulates cytoskeletal organization and cell function.