Figure 7.

Conceptual model of morphodynamics directed by F-actin bundles. Peripheral actin bundles, e.g., filopodia, template clustering of nascent adhesions and harbor PI3K signaling. The bundles direct lamellipodia, formed by Arp2/3-mediated actin polymerization, by setting the preferred sites and directions of protrusion initiation and propagation, respectively. An adhesion-based positive feedback loop (inset) amplifies PI3K signaling as the lamellipod spreads, promoting additional activation of Arp2/3 complex and formation of new actin bundles. The new bundles can direct initiation of distinct lamellipodia, seemingly branched from existing ones. Propagation of lamellipodia is self-limiting or metastable, and therefore, protrusion and PI3K signaling cease, and the lamellipodia at least partially retract but typically leave the F-actin bundles intact. Hence, the cycle can repeat, sometimes as a series of traveling protrusion waves.