title: β3 integrin-mediated spreading induced by matrix-bound BMP-2 controls Smad signaling in a stiffness-independent manner.
abstract: Understanding how cells integrate multiple signaling pathways to achieve specific cell differentiation is a challenging question in cell biology. We have explored the physiological presentation of BMP-2 by using a biomaterial that harbors tunable mechanical properties to promote localized BMP-2 signaling. We show that matrix-bound BMP-2 is sufficient to induce β3 integrin-dependent C2C12 cell spreading by overriding the soft signal of the biomaterial and impacting actin organization and adhesion site dynamics. In turn, αvβ3 integrin is required to mediate BMP-2-induced Smad signaling through a Cdc42-Src-FAK-ILK pathway. β3 integrin regulates a multistep process to control first BMP-2 receptor activity and second the inhibitory role of GSK3 on Smad signaling. Overall, our results show that BMP receptors and β3 integrin work together to control Smad signaling and tensional homeostasis, thereby coupling cell adhesion and fate commitment, two fundamental aspects of developmental biology and regenerative medicine.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U823, Institut Albert Bonniot, 38042 Grenoble, France Centre National de la Recherche Scientifique, Equipe de Recherche Labellisée 5284, 38042 Grenoble, France Université Grenoble Alpes, 38041 Grenoble, France Centre National de la Recherche Scientifique UMR 5628, Laboratoire des Matériaux et du Génie Physique, Institute of Technology, 38016 Grenoble, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Fourel
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U823, Institut Albert Bonniot, 38042 Grenoble, France Centre National de la Recherche Scientifique, Equipe de Recherche Labellisée 5284, 38042 Grenoble, France Université Grenoble Alpes, 38041 Grenoble, France Centre National de la Recherche Scientifique UMR 5628, Laboratoire des Matériaux et du Génie Physique, Institute of Technology, 38016 Grenoble, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Valat
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U823, Institut Albert Bonniot, 38042 Grenoble, France Centre National de la Recherche Scientifique, Equipe de Recherche Labellisée 5284, 38042 Grenoble, France Université Grenoble Alpes, 38041 Grenoble, France.
authors.forename: Eva
authors.initials: E
authors.lastname: Faurobert
authors.affiliation: Centre National de la Recherche Scientifique UMR 5628, Laboratoire des Matériaux et du Génie Physique, Institute of Technology, 38016 Grenoble, France.
authors.forename: Raphael
authors.initials: R
authors.lastname: Guillot
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U823, Institut Albert Bonniot, 38042 Grenoble, France Centre National de la Recherche Scientifique, Equipe de Recherche Labellisée 5284, 38042 Grenoble, France Université Grenoble Alpes, 38041 Grenoble, France.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Bourrin-Reynard
authors.affiliation: Centre National de la Recherche Scientifique UMR 5628, Laboratoire des Matériaux et du Génie Physique, Institute of Technology, 38016 Grenoble, France.
authors.forename: Kefeng
authors.initials: K
authors.lastname: Ren
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U823, Institut Albert Bonniot, 38042 Grenoble, France Université Grenoble Alpes, 38041 Grenoble, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Lafanechère
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U823, Institut Albert Bonniot, 38042 Grenoble, France Centre National de la Recherche Scientifique, Equipe de Recherche Labellisée 5284, 38042 Grenoble, France Université Grenoble Alpes, 38041 Grenoble, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Planus
authors.affiliation: Centre National de la Recherche Scientifique UMR 5628, Laboratoire des Matériaux et du Génie Physique, Institute of Technology, 38016 Grenoble, France corinne.albiges-rizo@ujf-grenoble.fr catherine.picart@grenoble-inp.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Picart
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U823, Institut Albert Bonniot, 38042 Grenoble, France Centre National de la Recherche Scientifique, Equipe de Recherche Labellisée 5284, 38042 Grenoble, France Université Grenoble Alpes, 38041 Grenoble, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Albiges-Rizo
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D039661:Integrin beta3 / Q000378:metabolism*; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D055396:Bone Morphogenetic Protein 2; D051417:Focal Adhesion Kinase 1; D039302:Integrin alphaVbeta3; D039661:Integrin beta3; D017346:Protein Serine-Threonine Kinases; D051785:Smad Proteins; D020764:cdc42 GTP-Binding Protein; D019061:src-Family Kinases; D000099200:Scaffold Protein ILK; C525719:Bmp2 protein, mouse; C496051:Ptk2 protein, mouse