Surface densities prewet a near-critical membrane

Significance Proteins capable of separating into three-dimensional liquid droplets in the cytoplasm and nuclei of cells sometimes assemble in a two-dimensional form at membranes. These surface densities, enriched in specific proteins and lipids, often play decisive roles in cell signaling and membrane organization. Here a theoretical approach suggests that surface densities resemble prewet surface phases held together through a combination of two-dimensional membrane-mediated forces and three-dimensional protein interactions. The emergent physics of these liquid surface phases enable their roles both as dynamic scaffolds and as cooperative switches that propagate signals between the membrane and bulk. Recent work has highlighted roles for thermodynamic phase behavior in diverse cellular processes. Proteins and nucleic acids can phase separate into three-dimensional liquid droplets in the cytoplasm and nucleus and the plasma membrane of animal cells appears tuned close to a two-dimensional liquid–liquid critical point. In some examples, cytoplasmic proteins aggregate at plasma membrane domains, forming structures such as the postsynaptic density and diverse signaling clusters. Here we examine the physics of these surface densities, employing minimal simulations of polymers prone to phase separation coupled to an Ising membrane surface in conjunction with a complementary Landau theory. We argue that these surface densities are a phase reminiscent of prewetting, in which a molecularly thin three-dimensional liquid forms on a usually solid surface. However, in surface densities the solid surface is replaced by a membrane with an independent propensity to phase separate. We show that proximity to criticality in the membrane dramatically increases the parameter regime in which a prewetting-like transition occurs, leading to a broad region where coexisting surface phases can form even when a bulk phase is unstable. Our simulations naturally exhibit three-surface phase coexistence even though both the membrane and the polymer bulk only display two-phase coexistence on their own. We argue that the physics of these surface densities may be shared with diverse functional structures seen in eukaryotic cells.