title: Evidence of a large-scale mechanosensing mechanism for cellular adaptation to substrate stiffness.
abstract: Cell migration plays a major role in many fundamental biological processes, such as morphogenesis, tumor metastasis, and wound healing. As they anchor and pull on their surroundings, adhering cells actively probe the stiffness of their environment. Current understanding is that traction forces exerted by cells arise mainly at mechanotransduction sites, called focal adhesions, whose size seems to be correlated to the force exerted by cells on their underlying substrate, at least during their initial stages. In fact, our data show by direct measurements that the buildup of traction forces is faster for larger substrate stiffness, and that the stress measured at adhesion sites depends on substrate rigidity. Our results, backed by a phenomenological model based on active gel theory, suggest that rigidity-sensing is mediated by a large-scale mechanism originating in the cytoskeleton instead of a local one. We show that large-scale mechanosensing leads to an adaptative response of cell migration to stiffness gradients. In response to a step boundary in rigidity, we observe not only that cells migrate preferentially toward stiffer substrates, but also that this response is optimal in a narrow range of rigidities. Taken together, these findings lead to unique insights into the regulation of cell response to external mechanical cues and provide evidence for a cytoskeleton-based rigidity-sensing mechanism.
authors.affiliation: Laboratoire Matière et Systèmes Complexes, Centre National de la Recherche Scientifique Unité Mixte de Recherche, 7057, Université Paris Diderot, 75205 Paris Cedex 13, France.
authors.forename: Léa
authors.initials: L
authors.lastname: Trichet
authors.forename: Jimmy
authors.initials: J
authors.lastname: Le Digabel
authors.forename: Rhoda J
authors.initials: RJ
authors.lastname: Hawkins
authors.forename: Sri Ram Krishna
authors.initials: SR
authors.lastname: Vedula
authors.forename: Mukund
authors.initials: M
authors.lastname: Gupta
authors.forename: Claire
authors.initials: C
authors.lastname: Ribrault
authors.forename: Pascal
authors.initials: P
authors.lastname: Hersen
authors.forename: Raphaël
authors.initials: R
authors.lastname: Voituriez
authors.forename: Benoît
authors.initials: B
authors.lastname: Ladoux
mesh_terms: D000199:Actins / Q000502:physiology; D000222:Adaptation, Physiological; D000818:Animals; D055592:Biophysical Phenomena; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology; D004548:Elasticity; D022001:Focal Adhesions / Q000502:physiology; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D051381:Rats; D013314:Stress, Mechanical; D013499:Surface Properties
chemical_list: D000199:Actins