Activity-InducedDroplet Inversion in MulticomponentLiquid–Liquid Phase Separation

Liquid–liquid phase separation (LLPS) is a vital process in forming membrane-free organelles, crucial for cell physiology and recently gaining significant attention. However, the effects of nonequilibrium factors, which are common in real life, on the process of LLPS have not been fully explored. To address this issue, we developed a model for nonequilibrium phase separation involving three components (A, B, and C) by integrating a nonequilibrium term into the chemical potential for active component B. We find significant changes in the morphology and dynamics of nonequilibrium phase-separated droplets compared to their equilibrium counterparts. Remarkably, with a large enough activity, the B-A-C structure (B at the center, surrounded by A, then enveloped by C) under equilibrium conditions may change to a C-A-B structure. Further simulations give a global picture of the system under both active and passive conditions, revealing the shifts of the phase boundaries and unraveling the effect of activity on different droplet structures. We derived an effective free energy for the active LLPS system to provide a qualitative understanding of our observations. Our study presents a basic model for nonequilibrium phase separation processes, providing crucial insights into LLPS alongside intracellular nonequilibrium phenomena.