Actin polymerization and intracellular solvent flow in cell surface blebbing.
The cortical actin gel of eukaryotic cells is postulated to control cell surface activity. One type of protrusion that may offer clues to this regulation are the spherical aneurysms of the surface membrane known as blebs. Blebs occur normally in cells during spreading and alternate with other protrusions, such as ruffles, suggesting similar protrusive machinery is involved. We recently reported that human melanoma cell lines deficient in the actin filament cross-linking protein, ABP-280, show prolonged blebbing, thus allowing close study of blebs and their dynamics. Blebs expand at different rates of volume increase that directly predict the final size achieved by each bleb. These rates decrease as the F-actin concentration of the cells increase over time after plating on a surface, but do so at lower concentrations in ABP-280 expressing cells. Fluorescently labeled actin and phalloidin injections of blebbing cells indicate that a polymerized actin structure is not present initially, but appears later and is responsible for stopping further bleb expansion. Therefore, it is postulated that blebs occur when the fluid-driven expansion of the cell membrane is sufficiently rapid to initially outpace the local rate of actin polymerization. In this model, the rate of intracellular solvent flow driving this expansion decreases as cortical gelation is achieved, whether by factors such as ABP-280, or by concentrated actin polymers alone, thereby leading to decreased size and occurrence of blebs. Since the forces driving bleb extension would always be present in a cell, this process may influence other cell protrusions as well.
Cunningham
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Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
D000199:Actins / Q000032:analysis / Q000378:metabolism* / Q000648:ultrastructure*; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure*; D003285:Contractile Proteins / Q000172:deficiency / Q000378:metabolism; D064448:Filamins; D006801:Humans; D007700:Kinetics; D008545:Melanoma; D008840:Microfilament Proteins / Q000172:deficiency / Q000378:metabolism; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video / Q000379:methods; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000199:Actins; D002352:Carrier Proteins; D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins