A mathematical model for bleb expansion clarifies a role for TalA in regulating blebbing

Eukaryotic cells, such as cancer and immune cells, migrate using either pressure-driven blebs or actin polymerization driven pseudopods, with cells preferring to bleb in confined environments where high protrusion forces are required for movement. Blebbing involves a separation of the cell membrane from the cortex, via the detachment of membrane-to-cortex linker proteins. The detached membrane then expands and stabilizes into a spherical cap as a new cortex is formed beneath the protruded membrane while the old one is completely degraded. The role of linker proteins in blebbing has mostly been associated with directing blebs to the leading edge of the cell, where linker enrichment is low, suggesting that cells devoid of linker proteins will bleb profusely. However, experimental work in this study involving talA null chemotaxing Dictyostelium discoideum cells shows the opposite effect, pointing to an alternative role for TalA. Our quantitative analysis of bleb size and frequency reveals that talA null cells produce fewer and smaller blebs in confined environments, pointing to a reduction in their intracellular pressure. A mathematical model of bleb expansion developed and validated with our experimental data supports the hypothesis that linker proteins help the cell maintain intracellular pressure during blebbing by limiting changes to its surface area when pressurized. Our model also identifies elastic and viscous properties of the cell, the assembly rate of the new cortex and disassembly rate of the old cortex as key modulators of change in bleb size induced by weakening the strength of membrane to cortex attachment.