Force-insensitive myosin-I enhances endocytosis robustness through actin network-scale collective ratcheting.

Force production by type-I myosins influences endocytic progression in many cell types. Because different myosin-I isoforms exhibit distinct force-dependent kinetic properties, it is important to investigate how these properties affect endocytic outcomes, and the mechanisms through which myosin-I contributes to endocytosis. To this end, we adapted our agent-based simulations of endocytic actin networks and incorporated nonprocessive, single-headed myosin motors at the base of the endocytic pit. We varied the unbinding rate and the force dependence of myosin unbinding. Our results revealed that the inclusion of myosin motors facilitated endocytic internalization, but only under kinetic regimes with rapid and less force-sensitive unbinding. Conversely, slow or strongly force-dependent unbinding impeded endocytic progression. As membrane tension increased, the boundary between assistive and inhibitory phases shifted, allowing the myosins to assist over larger regions of the kinetic landscape. Myosin-I's contribution to internalization could not be explained by direct force transduction or increased actin assembly. Instead, the myosins collectively bolstered the robustness of internalization by limiting pit retraction.