Surface Phases in Polymer Mixtures and Critical Membranes*

Proteins, RNA, and DNA phase-separate into liquid-like droplets in the 3D cytoplasm and nucleus. In 2D, lipids forming the plasma membrane are suggested to lie near a miscibility critical point below which they separate into coexisting liquid phases. Some phase-separated structures in the neuronal and immune synapse exclusively localize to the plasma memebrane. These structures are enriched in components that strongly partition into one of the membrane phases, and polymer domains often co-localize with particular membrane components. Here we explore the physical underpinnings of these domains. Using lattice Monte-Carlo simulations and a minimal Landau theory we find that surface-localized protein droplets are best described as prewet – a 2D phase of both 2D and 3D components which is stable outside of 3D coexistence regions. Criticality in the membrane greatly expands the prewet region of the phase diagram, within which lipid and protein components phase separate together. The underlying phase diagram exhibits coexistence of up to 3 unique surface phases at the membrane. Our theoretical results make concrete predictions for experiments in synthetic systems and explain a range of previous observations across biology