Three-dimensional morphodynamics simulations of macropinocytic cups

Abstract

*Macropinocytosis is non-specific uptake of the extracellular fluid playing ubiquitous roles in cell growth, immune-surveillance as well as virus entry. Despite its widespread occurrence, it remains unclear how its initial cup-shaped plasma membrane extensions forms without external physical support as in phagocytosis or curvature inducing proteins as in clathrin-mediated endocytosis. Here, by developing a novel computational framework that describes the coupling between bistable reaction-diffusion processes of active signaling patches and membrane deformation, we demonstrate that protrusive force localized to the edge of the patches can give rise to the self-enclosing cup structure without further assumption of local bending or contraction. Efficient uptake requires an appropriate balance between the patch size and the magnitude of protrusive force relative to the cortical tension. Furthermore, our model exhibits a variety of known morphology dynamics including cyclic cup formation, coexistence and competition between multiple cups and cup splitting indicating that these complex morphologies self-organize through mutually dependent dynamics between the reaction-diffusion process and membrane deformation.