Dynein regulates cell migration depending on substrate rigidity

Abstract

The mechanical environment in combination with biochemical signaling is an important regulatory factor for cellular physiology including tissue development, cell motility and differentiation. Exerting a tractional force triggered by myosin-dependent cell contractility is known to be an indispensible element of cell migration in a mechanically stiff environment such as a 2D planar surface. However, a number of reports have argued that the requirement of myosin activity for cell migration is limited by cell type and the environment. In this study, we present evidence that dynein, a minus end-directed microtubule motor, plays a central role in cell migration in the absence of tractional force. Interfering with the dynein activity through a dynein-specific inhibitor, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), dramatically inhibited 2D migration of the fibroblast when cell contractility was blocked by Rho kinase or a myosin inhibitor, although EHNA itself did not affect cell migration. Cell migration in 3D soft collagen matrices, where the cell exerts a relatively low tractional force compared to that on a 2D stiff surface, is also profoundly inhibited by dynein intermediate chain (DIC) silencing regardless of the presence of myosin activity. In addition, DIC-silenced cells on a soft acrylamide surface show decreased migration without blockade of myosin activity. Taken together, our results suggest that dynein may be a primary regulatory factor for cell migration when a cell is in a mechanically low-tension environment, such as in a 3D matrix.