How cortical waves drive the fission of motile cells

Abstract:

Motile cells like macrophages, stem cells, or cancer cells show complex spatiotemporal pattern formation in the actin cytoskeleton. These patterns can be influenced by external cues like chemoattractants, which lead to directed movement. But they can also occur spontaneously, for example, as self-sustained actin oscillations or waves. Recently it has been shown that one of the main genetic determinants for actin waves in Dictyostelium discoideum is a homologue of the RasGAP NF1. While D. discoideum wildtype cells with an intact NF1 gene do not display any self-sustained cortical wave patterns, a strain with a single knockout of the NF1 gene exhibits fully developed traveling waves. In contrast to actin waves in common lab strains, these waves are more stable and travel in a highly persistent fashion. Upon collision with the cell boundary, they induce strong deformations of the cell shape. In larger cells, they may even lead to the formation of separate cell segments that eventually pinch off the mother cell (wave-driven cell fission). The resulting daughter cells move in a highly persistent fashion, reminiscent of keratocyte motion. Their substrate-attached membrane is completely covered by the driving wave segment. We compare our experimental observations to numerical solutions of a model that combines a noisy excitable reaction-diffusion system with a dynamic phase field for the cell shape and identify key factors that are required for wave-driven cell fission.