Competing elastic and viscous gradients determine directional cell migration

Abstract

Cell migration regulates central life processes including embryonic development, tissue regeneration, and tumor invasion. To establish the direction of migration, cells follow exogenous cues. Durotaxis, the directed cell migration towards elastic stiffness gradients, is the classical example of mechanical taxis. However, whether gradients of the relaxation properties in the extracellular matrix may also induce tactic responses (viscotaxis) is not well understood. Moreover, whether and how durotaxis and viscotaxis interact with each other has never been investigated. Here, we integrate clutch models for cell adhesions with an active gel theory of cell migration to reveal the mechanisms that govern viscotaxis. We show that viscotaxis is enabled by an asymmetric expression of cell adhesions that further polarize the intracellular motility forces to establish the cell front, similar to durotaxis. More importantly, when both relaxation and elastic gradients coexist, durotaxis appears more efficient in controlling directed cell migration, which we confirm with experimental results. However, the presence of opposing relaxation gradients to an elastic one can arrest or shift the migration direction. Our model rationalizes for the first time the mechanisms that govern viscotaxis and its competition with durotaxis through a mathematical model.

Keywords: Active gel models; Cell adhesion; Clutch model; Durotaxis; Mechanotransduction; Viscotaxis.