The Forces behind Directed Cell Migration

Directed cell migration is an essential building block of life, present when an embryo develops, a dendritic cell migrates toward a lymphatic vessel, or a fibrotic organ fails to restore its normal parenchyma. Directed cell migration is often guided by spatial gradients in a physicochemical property of the cell microenvironment, such as a gradient in chemical factors dissolved in the medium or a gradient in the mechanical properties of the substrate. Single cells and tissues sense these gradients, establish a back-to-front polarity, and coordinate the migration machinery accordingly. Central to these steps we find physical forces. In some cases, these forces are integrated into the gradient sensing mechanism. Other times, they transmit information through cells and tissues to coordinate a collective response. At any time, they participate in the cellular migratory system. In this review, we explore the role of physical forces in gradient sensing, polarization, and coordinating movement from single cells to multicellular collectives. We use the framework proposed by the molecular clutch model and explore to what extent asymmetries in the different elements of the clutch can lead to directional migration.