Force transmission during adhesion-independent migration

Bergert et al. use theoretical modelling and cell-based experiments to show that adhesion-independent cell migration is powered by nonspecific substrate friction, with smaller forces exerted compared with those of focal-adhesion-dependent movement. When cells move using integrin-based focal adhesions, they pull in the direction of motion with large, ∼100 Pa, stresses that contract the substrate1. Integrin-mediated adhesions, however, are not required for in vivo confined migration2. During focal adhesion-free migration, the transmission of propelling forces, and their magnitude and orientation, are not understood. Here, we combine theory and experiments to investigate the forces involved in adhesion-free migration. Using a non-adherent blebbing cell line as a model, we show that actin cortex flows drive cell movement through nonspecific substrate friction. Strikingly, the forces propelling the cell forward are several orders of magnitude lower than during focal-adhesion-based motility. Moreover, the force distribution in adhesion-free migration is inverted: it acts to expand, rather than contract, the substrate in the direction of motion. This fundamentally different mode of force transmission may have implications for cell–cell and cell–substrate interactions during migration in vivo.