title: Adhesion dynamics and durotaxis in migrating cells.
abstract: When tissue cells are plated on a flexible substrate, durotaxis, the directed migration of cells toward mechanically stiff regions, has been observed. Environmental mechanical signals are not only important in cell migration but also seem to influence all aspects of cell differentiation and development, including the metastatic process in cancer cells. Based on a theoretical model suggesting that this mechanosensation has a mechanical basis, we introduce a simple model of a cell by considering the contraction of F-actin bundles containing myosin motors (stress fibers) mediated by the movement of adhesions. We show that, when presented with a linear stiffness gradient, this simple model exhibits durotaxis. Interestingly, since stress fibers do not form on soft surfaces and since adhesion sliding occurs very slowly on hard surfaces, the model predicts that the expected cell velocity reaches a maximum at an intermediate stiffness. This prediction can be experimentally tested. We therefore argue that stiffness-dependent cellular adaptations (mechanosensation) and durotaxis are intimately related and may share a mechanical basis. We therefore identify the essential physical ingredients, which combined with additional biochemical mechanisms can explain durotaxis and mechanosensation in cells.
authors.affiliation: Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Harland
authors.forename: Sam
authors.initials: S
authors.lastname: Walcott
authors.forename: Sean X
authors.initials: SX
authors.lastname: Sun
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D003198:Computer Simulation; D006801:Humans; D055595:Mechanical Phenomena; D008954:Models, Biological; D022502:Stress Fibers / Q000378:metabolism