Cell morphogenesis via shape-guided self-propelled treadmilling actin waves

Actin dynamics mediate cell morphogenesis and motility. Actin filaments polymerise 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 biochemically regulated by signalling pathways. However, it remains unclear whether these signal-driven mechanisms alone are sufficient to regulate local actin polymerisation at cell protrusions. Here, we show that cell shape can also regulate actin dynamics. We found that arrays of actin filaments emerge widely in glioma cells and translocate as actin waves in the direction of polymerisation through treadmilling, i.e. directional polymerisation and disassembly. The arrival of actin waves at the cell periphery pushes the plasma membrane to form protrusions (filopodia and lamellipodia). Furthermore, actin waves accumulate at protrusions even in the absence of local signalling cues, similar to self-propelled particles (active particles) colliding with a boundary, thereby leading to further expansion of protrusions for cell polarisation and migration. The shape-guided actin accumulation constitutes a positive feedback interaction with actin-mediated cell protrusion and mediates an effective lateral inhibition, thereby conferring robustness to the classical pathway of cellular morphogenesis. Because actin filaments undergo treadmilling in various protrusions, we propose that the cell shape-guided and self-propelled movement is a basic property of treadmilling actin filaments that mediates robust cell morphogenesis and motility.