Cell morphogenesis via self-propelled treadmilling actin waves

Actin dynamics mediate cell morphogenesis and motility. Actin filaments polymerize outward at cell protrusions such as the leading edge of migrating cells, thereby pushing the membrane to protrude. The current paradigm explains that actin dynamics are regulated by biochemical signaling pathways. However, it is unclear how cells can form protrusions even without local signaling cues. We found that arrays of treadmilling actin filaments emerge widely in migrating cells and translocate in the direction of polymerization as actin waves. Their arrival at the cell periphery pushed the plasma membrane to protrude. Furthermore, they accumulate at protrusions without local signaling cues, similar to self-propelled particles colliding with a boundary. This leads to further expansion of the protrusions, promoting cell polarization and migration. We propose that the self-propelled actin waves drive robust formation of protrusions during spontaneous cell morphogenesis, through a positive feedback interaction with actin-mediated protrusion and effective lateral inhibition.

肌动蛋白动态（actin dynamics）介导细胞形态发生与细胞运动。肌动蛋白丝（actin filaments）在迁移细胞前沿等细胞突起（cell protrusions）处向外聚合，进而推动细胞膜向外凸起。当前主流范式认为，肌动蛋白动态由生化信号通路（biochemical signaling pathways）调控。然而，尚不清楚细胞在缺乏局部信号提示的情况下如何形成突起。我们的研究发现，踏车式肌动蛋白丝（treadmilling actin filaments）阵列广泛存在于迁移细胞中，并随肌动蛋白波（actin waves）沿聚合方向移位。当其抵达细胞外周时，会推动质膜（plasma membrane）形成凸起。此外，这些肌动蛋白丝会在突起处聚集，无需依赖局部信号提示，这一现象与碰撞边界的自驱动粒子（self-propelled particles）类似。该过程会进一步促进突起扩张，推动细胞极化与迁移。我们提出，自驱动肌动蛋白波可通过与肌动蛋白介导的凸起形成正反馈（positive feedback）相互作用，并借助有效的侧向抑制（lateral inhibition），在自发性细胞形态发生过程中驱动突起的稳健形成。