Mechanochemical feedback between confinement and actin crosslinking drives the shape dynamics of liquid-like droplets

Abstract

Abstract Several actin-binding proteins form phase-separated condensates that promote actin filament assembly and bundling. However, the mechanism by which crosslinker multivalency, actin growth, and condensate mechanics regulate actin organization and droplet shape is not well understood. Here, using a combination of agent-based simulations and experiments, we show that a dynamically deformable droplet interface enables the emergence of tightly-bundled actin rings and weakly-bundled actin discs. We find that crosslinked bundle thickness and droplet diameter follow a power law, consistent with measurements in condensates formed by vasodilator-stimulated phosphoprotein. In addition, the dynamics of droplet deformation exhibit a dynamic snapping behavior that depends on droplet surface tension and crosslinker binding kinetics. We assess the generalizability of these predictions in condensates formed by lamellipodin and RGG. Together, these results indicate that mechanochemical feedback between droplet interfacial mechanics and crosslinker multivalency tunes actin organization and controls the dynamics of droplet deformation driven by actin networks.