Mechanical Regulation of Actin Network Dynamics in Migrating Cells

Abstract

Cell migration is fundamental to various physiological processes, including metastasis, wound healing and tissue development. The complex processes involved in cell migration; polymerization, adhesion, and retraction, are mediated by highly orchestrated structure-function interactions that occur within the actin cytoskeletal structure. Thus understanding how migrating cells regulate the global dynamics of their cytoskeletal components, which result from rather localized protein-protein interactions, is fundamental to elucidating the mechanisms of cell motility. The objective of this review is to explore the mechanical regulation of actin network dynamics in migrating cells, and to discuss its regulatory role in cell migration. Specifically, we examine the various mechanical forces involved in cell migration, and how they couple with biomechanical factors to spatiotemporally regulate the dynamics of the actin cytoskeleton during cell motility. Two aspects of actin network dynamics are addressed, namely, network turnover by polymerization and depolymerization, and network flow resulting from actomyosin activity. We begin by highlighting the fundamental features of actin network dynamics in migrating cells. We then examine the coupling relationship between actin network flow and traction forces, as well as the mechanism underlying the regulation of traction forces by actin network flow. Finally, we integrate the various motility processes into a mechanical pathway in order to elucidate the importance of mechanical regulation of actin network dynamics to cell migration.