Dissection of amoeboid movement into two mechanically distinct modes

The current dominant model of cell locomotion proposes that actin polymerization pushes against the membrane at the leading edge producing filopodia and lamellipodia that move the cell forward. Despite its success, this model does not fully explain the complex process of amoeboid motility, such as that occurring during embryogenesis and metastasis. Here, we show that Dictyostelium cells moving in a physiological milieu continuously produce 'blebs' at their leading edges, and demonstrate that focal blebbing contributes greatly to their locomotion. Blebs are well-characterized spherical hyaline protrusions that occur when a patch of cell membrane detaches from its supporting cortex. Their formation requires the activity of myosin II, and their physiological contribution to cell motility has not been fully appreciated. We find that pseudopodia extension, cell body retraction and overall cell displacement are reduced under conditions that prevent blebbing, including high osmolarity and blebbistatin, and in myosin-II-null cells. We conclude that amoeboid motility comprises two mechanically different processes characterized by the production of two distinct cell-surface protrusions, blebs and filopodia-lamellipodia.