Lipids Facilitate Protein Assembly at Membranes through Prewetting

Proteins that assemble into condensates in solution can also condense into surface phase domains when a subset of condensate components are tethered to or interact with fluid membranes. These domains are dynamic, effectively two-dimensional, and considered “prewet” because they occur well outside of the coexistence region of the condensate system alone. We show that proximity to the membrane phase transition dramatically potentiates biopolymer prewetting through a combination of theory, simulation, and experiments in well-defined reconstituted systems. When taken into cells, we show that protein prewetting at the plasma membrane inner leaflet is sensitive to perturbations of plasma membrane composition. More generally, we speculate that prewetting at membranes represents a general protein assembly mechanism involved in a broad array of cell processes and sensitive to both membrane and protein properties.