Three-Dimensional Balance of Cortical Tension and Axial Contractility Enables Fast Amoeboid Migration

Abstract

Fast amoeboid migration requires cells to apply mechanical forces on their surroundings via transient adhesions. However, the mechanistic role of forces in controlling cell shape changes and cell migration speed remains largely unknown. To address these questions, we used three-dimensional force microscopy to measure the in-plane (tangential) and out-of-plane (normal) forces exerted by cells crawling on flat surfaces. From the measured normal forces, we estimated the cells’ cortical tension using a Young-Laplace's model. We examined chemotaxing wild-type Dictyostelium cells, as well as mutants with defects in contractility, internal F-actin crosslinking, and cortical integrity, and demonstrated that once the cells initiate their migration and polarize, they generate tangential traction forces by myosin II contractility, which requires an internal crosslinked F-actin network. Simultaneously, cortical tension provides an additional mechanism that generates the normal forces and that does not require myosin II. The 3-D pulling forces generated by both mechanisms are internally balanced by an increase in cytoplasmic pressure that allows cells to push down on their substrate without adhering to it. These compressive pressure-induced forces are not associated to adhesion sites, and may allow amoeboid cells to push off surrounding structures when migrating in complex three-dimensional environments. Our findings are consistent with a model in which the two force-generating cellular domains are mechanically connected by myosin I crosslinking that enables the communication of forces between the domains. Furthermore, we found that the balance between axial myosin II contractility and cortical tension is important to produce the cell shape changes needed for locomotion, as cell migration speed correlates with the ratio of the magnitudes of the tangential traction forces to the normal ones. These results reveal a novel role for 3-D cellular forces in establishing the efficiency of amoeboid cell movement.