A role for PaxB in regulating blebbing: experimental insights and theoretical perspectives from Dictyostelium discoideum

Eukaryotic cells migrate using pressure-driven blebs or actin polymerization driven pseudopods, with cells preferring to bleb in compressed environments where high protrusion forces are required for movement. In mammals, paxillin is a focal adhesion protein that acts as a scaffold, linking integrins to the actin cytoskeleton and recruiting signaling molecules that regulate adhesion, cytoskeletal remodeling, and migration. Dictyostelium possesses a paxillin ortholog, PaxB, which shares conserved domains with mammalian paxillin and participates in processes such as adhesion, cytokinesis, development, and chemotaxis. However, the role of PaxB in blebbing is not well understood. Our work combines experimental and theoretical methods to elucidate the role of PaxB in blebbing. We use an under-agarose assay to collect data on paxB$$^{-}$$ and wild-type cells under low and high compression and observe blebbing characteristics such as area and frequency. Our experimental results point to a role for PaxB in regulating the relative size of blebs in response to increased compression. Using a mathematical model of bleb expansion, we show that decreasing the assembly rate of the cortex during bleb formation leads to relatively larger blebs, thus providing a potential mechanism that replicates the mutant phenotype. Together, our experiments and theory suggest a new role of PaxB in bleb-based chemotaxis.