A mathematical model for bleb expansion clarifies the role of TalA and actin dynamics in regulating bleb size and frequency

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 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, recent experiments suggest that knocking out the linker protein, TalA, in Dictyostelium discoideum cells decreases the cells ability to bleb. Additionally, little is known about how actin dynamics during bleb stabilization affect bleb size. In this work, we analyze the size and frequency of blebs in wild type and talA null Dictyostelium discoideum cells chemotaxing under a light and heavy agarose block. Our analysis reveals that talA null cells produce fewer and smaller blebs in confined environments, suggesting that linker proteins help the cell maintain intracellular pressure during blebbing. A mathematical model of bleb expansion developed and validated with our experimental data supports this hypothesis and identifies the polymerization to depolymerization rate of actin in the reforming cortex as a key regulator of bleb size and retraction dynamics in a myosin II independent manner.