A Clockwork Bleb: cytoskeleton, calcium, and cytoplasmic fluidity

When the plasma membrane (PM) detaches from the underlying actin cortex, the PM expands according to intracellular pressure and a spherical membrane protrusion called a bleb is formed. This bleb retracts when the actin cortex is reassembled underneath the PM. Whereas this phenomenon seems simple at first glance, there are many interesting, unresolved cell biological questions in each process. For example, what is the membrane source to enlarge the surface area of the PM during rapid bleb expansion? What signals induce actin reassembly for bleb retraction, and how is cytoplasmic fluidity regulated to allow rapid membrane deformation during bleb expansion? Furthermore, emerging evidence indicates that cancer cells use blebs for invasion, but little is known about how molecules that are involved in bleb formation, expansion, and retraction are coordinated for directional amoeboid migration. In this review, we discuss the molecular mechanisms involved in the regulation of blebs, which have been revealed by various experimental systems.

Automated summary

When the plasma membrane detaches from the underlying actin cortex, it expands to form a spherical membrane protrusion called a bleb. The bleb retracts when the actin cortex is reassembled. Many unanswered questions remain regarding membrane source, actin reassembly signals, and cytoplasmic fluidity regulation during bleb formation. Additionally, the use of blebs by cancer cells for invasion and the coordination of molecules involved in bleb formation, expansion, and retraction for directional migration are areas of little current knowledge. In this review, molecular mechanisms of bleb regulation are discussed based on various experimental systems.