title: Mechanotransduction of shear stress occurs through changes in VE-cadherin and PECAM-1 tension: implications for cell migration.
abstract: Recent work has shown that cadherins at cell-cell junctions bear tensile forces. Using novel FRET-based tension sensors, we showed first that in response to shear stress, endothelial cells rapidly reduce mechanical tension on vascular endothelial (VE)-cadherin. Second, we observed a simultaneous increase in tension on platelet endothelial cell adhesion molecule (PECAM)-1, induced by an interaction with vimentin. In this commentary, we discuss how our results fit with existing data on cadherins as important mediators of mechanotransduction, in particular, in cell migration where mechanical tension across cadherins may communicate the direction of movement. The ability of PECAM-1 to bear mechanical tension may also be important in other PECAM-1 functions, such as leukocyte transmigration through the endothelium. Additionally, our observation that vimentin expression was required for PECAM-1 tension and mechanotransduction of fluid flow suggests that intermediate filaments are capable of transmitting tension. Overall, our results argue against models where an external force is passively transferred across the cytoskeleton, and instead suggest that cells actively respond to extracellular forces by modulating tension across junctional proteins.
authors.affiliation: a Department of Biomedical Engineering ; Virginia Commonwealth University ; Richmond , VA USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Conway
authors.affiliation: b Yale Cardiovascular Research Center ; Department of Internal Medicine (Section of Cardiovascular Medicine) and Departments of Cell Biology and Biomedical Engineering ; New Haven , CT USA.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002465:Cell Movement; D006801:Humans; D040542:Mechanotransduction, Cellular; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D013312:Stress, Physiological; D014746:Vimentin / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014746:Vimentin; D000099152:Cadherin 5
keywords: PECAM-1; VE-cadherin; cell-cell junctions; fluid shear stress; mechanotransduction; vimentin intermediate filaments