title: Mechanical checkpoint for persistent cell polarization in adhesion-naive fibroblasts.
abstract: Cell polarization is a fundamental biological process implicated in nearly every aspect of multicellular development. The role of cell-extracellular matrix contacts in the establishment and the orientation of cell polarity have been extensively studied. However, the respective contributions of substrate mechanics and biochemistry remain unclear. Here we propose a believed novel single-cell approach to assess the minimal polarization trigger. Using nonadhered round fibroblast cells, we show that stiffness sensing through single localized integrin-mediated cues are necessary and sufficient to trigger and direct a shape polarization. In addition, the traction force developed by cells has to reach a minimal threshold of 56 ± 1.6 pN for persistent polarization. The polarization kinetics increases with the stiffness of the cue. The polarized state is characterized by cortical actomyosin redistribution together with cell shape change. We develop a physical model supporting the idea that a local and persistent inhibition of actin polymerization and/or myosin activity is sufficient to trigger and sustain the polarized state. Finally, the cortical polarity propagates to an intracellular polarity, evidenced by the reorientation of the centrosome. Our results define the minimal adhesive requirements and quantify the mechanical checkpoint for persistent cell shape and organelle polarization, which are critical regulators of tissue and cell development.
authors.affiliation: Macromolecular Complexes in Living Cells, Unité Mixe de Recherche 7592, Institut Jacques Monod, Centre National de la Recherche Scientifique, University Paris VII, Paris, France. Electronic address: philippe.bun@embl.de.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bun
authors.affiliation: Macromolecular Complexes in Living Cells, Unité Mixe de Recherche 7592, Institut Jacques Monod, Centre National de la Recherche Scientifique, University Paris VII, Paris, France.
authors.forename: JunJun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Physical Chemistry Curie, Unité Mixte de Recherche 168, Institut Curie, Centre National de la Recherche Scientifique, University Paris VI, Paris, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Turlier
authors.affiliation: Macromolecular Complexes in Living Cells, Unité Mixe de Recherche 7592, Institut Jacques Monod, Centre National de la Recherche Scientifique, University Paris VII, Paris, France.
authors.forename: ZengZhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Macromolecular Complexes in Living Cells, Unité Mixe de Recherche 7592, Institut Jacques Monod, Centre National de la Recherche Scientifique, University Paris VII, Paris, France.
authors.forename: Karen
authors.initials: K
authors.lastname: Uriot
authors.affiliation: Physical Chemistry Curie, Unité Mixte de Recherche 168, Institut Curie, Centre National de la Recherche Scientifique, University Paris VI, Paris, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Joanny
authors.affiliation: Macromolecular Complexes in Living Cells, Unité Mixe de Recherche 7592, Institut Jacques Monod, Centre National de la Recherche Scientifique, University Paris VII, Paris, France. Electronic address: coppey.maite@ijm.univ-paris-diderot.fr.
authors.forename: Maïté
authors.initials: M
authors.lastname: Coppey-Moisan
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000205:Actomyosin / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D016764:Cell Polarity; D018385:Centrosome / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D016023:Integrins / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D058105:Polymerization; D013499:Surface Properties
chemical_list: D000199:Actins; D016023:Integrins; D000205:Actomyosin