title: Binding of ZO-1 to α5β1 integrins regulates the mechanical properties of α5β1-fibronectin links.
abstract: Fundamental processes in cell adhesion, motility, and rigidity adaptation are regulated by integrin-mediated adhesion to the extracellular matrix (ECM). The link between the ECM component fibronectin (fn) and integrin α5β1 forms a complex with ZO-1 in cells at the edge of migrating monolayers, regulating cell migration. However, how this complex affects the α5β1-fn link is unknown. Here we show that the α5β1/ZO-1 complex decreases the resistance to force of α5β1-fn adhesions located at the edge of migrating cell monolayers while also increasing α5β1 recruitment. Consistently with a molecular clutch model of adhesion, this effect of ZO-1 leads to a decrease in the density and intensity of adhesions in cells at the edge of migrating monolayers. Taken together, our results unveil a new mode of integrin regulation through modification of the mechanical properties of integrin-ECM links, which may be harnessed by cells to control adhesion and migration.
authors.affiliation: Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain.|University of Barcelona, 08028 Barcelona, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: González-Tarragó
authors.affiliation: Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Elosegui-Artola
authors.affiliation: IBDM, Institut de Biologie du Développement de Marseille, UMR 7288, 13009 Marseille, France.
authors.forename: Elsa
authors.initials: E
authors.lastname: Bazellières
authors.affiliation: Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain.|University of Barcelona, 08028 Barcelona, Spain.
authors.forename: Roger
authors.initials: R
authors.lastname: Oria
authors.affiliation: Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain.|University of Barcelona, 08028 Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Pérez-González
authors.affiliation: Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain rocacusachs@ub.edu.|University of Barcelona, 08028 Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Roca-Cusachs
mesh_terms: D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement; D003412:Cricetulus; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism* / Q000502:physiology; D016023:Integrins / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000502:physiology; D011485:Protein Binding; D062826:Zonula Occludens-1 Protein / Q000378:metabolism* / Q000502:physiology
chemical_list: C067625:FN1 protein, human; D005353:Fibronectins; D039081:Integrin alpha5beta1; D016023:Integrins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein