Spatiotemporal coordination of contraction, pressure and retraction during bleb-mediated migration

Blebbing is a pressure-driven form of membrane protrusion that occurs in both physiological and pathological situations. Due to the short-lived nature of blebs, studies have commonly coupled cellular experiments with mathematical modeling. The majority of current models deal with the life cycle of a prototypical bleb, consisting of three phases --- nucleation, expansion, and retraction. Bleb nucleation occurs upon separation of the membrane-cortex linkage and results in pressure-driven flow of cytosolic fluid. This flow is responsible for the growth of a spherical membrane protrusion, otherwise known as an expanded bleb. Retraction of the bleb occurs in a myosin-II dependent manner and involves the reassembly of the cortex underneath the bleb membrane and linkage of the membrane and cortex. Although blebbing can be described by these three phases, the majority of models focus on the initial phases of blebbing with much less attention given to the retraction phase. Further investigation of the physical and molecular interactions during the retraction phase could be important in better understanding of blebs that diverge from a prototypical life-cycle. For example, blebs in migrating cells are observed to forgo retraction and instead experience subsequent expansion events. By taking an integrative look at the biophysics during the stages of blebbing, we hypothesize that sustained bleb-based migration through subsequent expansion events could be explained by coordination of squeezing at the cell rear, spatiotemporal dynamics of intracellular pressure and inhibition of retraction at the cell front.--Author's abstract