title: Rho GTPases link cellular contractile force to the density and distribution of nanoscale adhesions.
abstract: The ability of cells to adhere and to exert contractile forces governs their capacity to move within an organism. The cytoskeletal regulators of the Rho GTPase proteins are involved in control of the contractile forces of cells. To elucidate the basis of cell migration, we analyzed contractile forces and nanoscale adhesion-related particles in single cells expressing constitutively active variants of Rho GTPases by using traction-force microscopy and ultra-high-resolution stimulated emission depletion microscopy, respectively. RhoAV14 induced large increases in the contractile forces of single cells, with Rac1L61 and RhoDV26 having more moderate effects. The RhoAV14- and RhoDV26-induced forces showed similar spatial distributions and were accompanied by reduced or unaltered cell spreading. In contrast, the Rac1L61-induced force had different, scattered, force distributions that were linked to increased cell spreading. All three of these Rho GTPase activities caused a loss of thick stress fibers and focal adhesions and a more homogenous distribution of nanoscale adhesion-related particles over the ventral surface of the cells. Interestingly, only RhoAV14 increased the density of these particles. Our data suggest a Rac1-specific mode for cells to generate contractile forces. Importantly, increased density and a more homogenous distribution of these small adhesion-related particles promote cellular contractile forces.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Nobels v. 16, Box 280, Karolinska Institutet, SE-171 77 Stockholm, Sweden. annica.gad@ki.se
authors.forename: Annica K B
authors.initials: AK
authors.lastname: Gad
authors.forename: Daniel
authors.initials: D
authors.lastname: Rönnlund
authors.forename: Alexander
authors.initials: A
authors.lastname: Spaar
authors.forename: Andrii A
authors.initials: AA
authors.lastname: Savchenko
authors.forename: Gabor
authors.initials: G
authors.lastname: Petranyi
authors.forename: Hans
authors.initials: H
authors.lastname: Blom
authors.forename: Laszlo
authors.initials: L
authors.lastname: Szekely
authors.forename: Jerker
authors.initials: J
authors.lastname: Widengren
authors.forename: Pontus
authors.initials: P
authors.lastname: Aspenström
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002468:Cell Physiological Phenomena / Q000502:physiology*; D022001:Focal Adhesions / Q000378:metabolism; D051379:Mice; D008853:Microscopy; D041681:NIH 3T3 Cells; D013552:Swine; D020830:rac1 GTP-Binding Protein / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000502:physiology
chemical_list: C491334:Rhod protein, mouse; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein