Stimulation of integrin-mediated cell contractility by fibronectin polymerization.
Ligation of integrins with extracellular matrix molecules induces the clustering of actin and actin-binding proteins to focal adhesions, which serves to mechanically couple the matrix with the cytoskeleton. During wound healing and development, matrix deposition and remodeling may impart additional tensile forces that modulate integrin-mediated cell functions, including cell migration and proliferation. We have utilized the ability of cells to contract floating collagen gels to determine the effect of fibronectin polymerization on mechanical tension generation by cells. Our data indicate that fibronectin polymerization promotes cell spreading in collagen gels and stimulates cell contractility by a Rho-dependent mechanism. Fibronectin-stimulated contractility was dependent on integrin ligation; however, integrin ligation by fibronectin fragments was not sufficient to induce either tension generation or cell spreading. Furthermore, treatment of cells with polyvalent RGD peptides or pre-polymerized fibronectin did not stimulate cell contractility. Fibronectin-induced contractility was blocked by agents that inhibit fibronectin polymerization, suggesting that the process of fibronectin polymerization is critical in triggering cytoskeletal tension generation. These data indicate that Rho-mediated cell contractility is regulated by the process of fibronectin polymerization and suggest a novel mechanism by which extracellular matrix fibronectin regulates cytoskeletal organization and cell function.
Hocking
D C
DC
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York 14642, USA. denise_hocking@urmc.rochester.edu
Sottile
J
J
Langenbach
K J
KJ
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D048429:Cell Size / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen; D003599:Cytoskeleton / Q000502:physiology; D004622:Embryo, Mammalian; D005109:Extracellular Matrix / Q000502:physiology; D005353:Fibronectins / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D005780:Gelatin / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013314:Stress, Mechanical; D013718:Tensile Strength
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D016023:Integrins; D009842:Oligopeptides; D011994:Recombinant Proteins; C047981:arginyl-glycyl-aspartic acid; D005780:Gelatin; D003094:Collagen