Competition between phase interface and activity-induced heterogeneity in nonequilibrium cellular uptake

Abstract The dynamic interplay between activity and phase separation is essential to a broad range of physiological functions. Yet a fundamental understanding of the impact of this nonequilibrium physical process on cellular uptake remains elusive. Combining simulations, theory and experimental discussions, here we explore this crucial process by elucidating the nonequilibrium interactions of active particles with phase-separated cell membranes. In stark contrast to the generally considered homogeneous characteristic of membranes, our simulations demonstrate that the activity generates remarkable heterogeneity of membrane density and active tension along a neck zone, which becomes more eminent at the interface between two phase domains. A theoretical model is further developed to reveal that the competition between the neck tip of the heterogeneous membrane and the phase interface critically governs the uptake of active particles. It yields theoretical diagrams of different characteristic dynamic states related to the uptake in various parameter spaces, as confirmed by systematic simulations. The agreement between theoretical model and simulations establishes the physical basis for this phase-interface-regulated cellular uptake out of equilibrium, which bears broad implications in understanding diverse behaviors of living activities as delineated in the experimental discussions. More generally, our results provide a framework for understanding active, nonequilibrium interactions and physics at cellular interfaces in a broad biological and biotechnological context.