title: The integrin expression profile modulates orientation and dynamics of force transmission at cell-matrix adhesions.
abstract: Integrin adhesion receptors connect the extracellular matrix (ECM) to the cytoskeleton and serve as bidirectional mechanotransducers. During development, angiogenesis, wound healing and cancer progression, the relative abundance of fibronectin receptors, including integrins α5β1 and αvβ3, changes, thus altering the integrin composition of cell-matrix adhesions. Here, we show that enhanced αvβ3 expression can fully compensate for loss of α5β1 and other β1 integrins to support outside-in and inside-out force transmission. α5β1 and αvβ3 each mediate actin cytoskeletal remodeling in response to stiffening or cyclic stretching of the ECM. Likewise, α5β1 and αvβ3 support cellular traction forces of comparable magnitudes and similarly increase these forces in response to ECM stiffening. However, cells using αvβ3 respond to lower stiffness ranges, reorganize their actin cytoskeleton more substantially in response to stretch, and show more randomly oriented traction forces. Centripetal traction force orientation requires long stress fibers that are formed through the action of Rho kinase (ROCK) and myosin II, and that are supported by α5β1. Thus, altering the relative abundance of fibronectin-binding integrins in cell-matrix adhesions affects the spatiotemporal organization of force transmission.
authors: Division of Toxicology, Leiden Academic Center for Drug Research, Leiden University, 2333 CC Leiden, the Netherlands h.e.balcioglu@lacdr.leidenuniv.nl e.danen@lacdr.leidenuniv.nl.
authors: Hayri E
authors: HE
authors: Balcioglu
authors: Physics of Life Processes, Kamerlingh Onnes-Huygens Laboratory, Leiden University, 2333 CC Leiden, the Netherlands.
authors: Hedde
authors: H
authors: van Hoorn
authors: Physics of Life Processes, Kamerlingh Onnes-Huygens Laboratory, Leiden University, 2333 CC Leiden, the Netherlands.
authors: Dominique M
authors: DM
authors: Donato
authors: Physics of Life Processes, Kamerlingh Onnes-Huygens Laboratory, Leiden University, 2333 CC Leiden, the Netherlands.
authors: Thomas
authors: T
authors: Schmidt
authors: Division of Toxicology, Leiden Academic Center for Drug Research, Leiden University, 2333 CC Leiden, the Netherlands h.e.balcioglu@lacdr.leidenuniv.nl e.danen@lacdr.leidenuniv.nl.
authors: Erik H J
authors: EH
authors: Danen
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000378:metabolism; D001696:Biomechanical Phenomena; D021982:Cell-Matrix Junctions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D039081:Integrin alpha5beta1 / Q000235:genetics / Q000378:metabolism*; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism*; D024462:Myosin Type II / Q000378:metabolism; D011485:Protein Binding; D054460:rho-Associated Kinases
chemical_list: D039081:Integrin alpha5beta1; D039302:Integrin alphaVbeta3; D054460:rho-Associated Kinases; D024462:Myosin Type II
keywords: Actin cytoskeleton; Cell–matrix adhesion; Fibronectin; Mechanotransduction; ROCK; Rho kinase; Traction force; β1 integrin; β3 integrin