title: Rho mediates the shear-enhancement of endothelial cell migration and traction force generation.
abstract: The migration of vascular endothelial cells in vivo occurs in a fluid dynamic environment due to blood flow, but the role of hemodynamic forces in cell migration is not yet completely understood. Here we investigated the effect of shear stress, the frictional drag of blood flowing over the cell surface, on the migration speed of individual endothelial cells on fibronectin-coated surfaces, as well as the biochemical and biophysical bases underlying this shear effect. Under static conditions, cell migration speed had a bell-shaped relationship with fibronectin concentration. Shear stress significantly increased the migration speed at all fibronectin concentrations tested and shifted the bell-shaped curve upwards. Shear stress also induced the activation of Rho GTPase and increased the traction force exerted by endothelial cells on the underlying substrate, both at the leading edge and the rear, suggesting that shear stress enhances both the frontal forward-pulling force and tail retraction. The inhibition of a Rho-associated kinase, p160ROCK, decreased the traction force and migration speed under both static and shear conditions and eliminated the shear-enhancement of migration speed. Our results indicate that shear stress enhances the migration speed of endothelial cells by modulating the biophysical force of tractions through the biochemical pathway of Rho-p160ROCK.
authors.affiliation: Department of Bioengineering and The Whitaker Institute of Biomedical Engineering, University of California at San Diego, La Jolla, California 92093-0427, USA.
authors.forename: Yan-Ting
authors.initials: YT
authors.lastname: Shiu
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: William A
authors.initials: WA
authors.lastname: Marganski
authors.forename: Shunichi
authors.initials: S
authors.lastname: Usami
authors.forename: Martin A
authors.initials: MA
authors.lastname: Schwartz
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Wang
authors.forename: Micah
authors.initials: M
authors.lastname: Dembo
authors.forename: Shu
authors.initials: S
authors.lastname: Chien
mesh_terms: D000818:Animals; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013314:Stress, Mechanical; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D005353:Fibronectins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein