A phase diagram for active phase separation on lipid membranes

Two-state molecules such as phosphoinositides and small GTPases play essential roles in membrane mechanics, signaling, and vesicle trafficking. Switching between their active and inactive states is driven by enzyme-catalyzed, energy-consuming reactions. Enzyme-mediated feedback loops promote the formation of membrane domains enriched in one state, leading to nonequilibrium phase separation. Starting from a minimal chemical reaction network, we develop a mean-field theory and construct the corresponding phase diagram. Crucially, phase coexistence here is governed not by thermodynamic parameters, but by kinetic rates and concentrations. The system exhibits metastable homogeneous states that undergo spontaneous nucleation and coarsening, driven by effective interfacial tension. We analyze the nucleation dynamics accounting for multiplicative noise from chemical reactions, and derive explicit expressions for the critical nucleus size and interfacial tension in terms of rates and concentrations. Analytical predictions, confirmed by simulations, identify tunable biochemical parameters that control enzyme-driven phase separation on membranes.