Transmembrane coupling drives the growth of liquid-like protein condensates.

Timely and precise assembly of protein complexes on membrane surfaces is essential to the physiology of living cells. Recently, protein phase separation has been observed at cellular membranes, suggesting it may play a role in the assembly of protein complexes. Inspired by these findings, we observed that two-dimensional protein condensates on one side of a planar suspended membrane spontaneously colocalized with those on the opposite side. How might this phenomenon contribute to the assembly of stable transmembrane complexes? To address this question, we examined the diffusion and growth of two-dimensional protein condensates on both sides of membranes. Our results reveal that transmembrane coupling of protein condensates on opposite sides of the membrane slows down condensate diffusion and promotes condensate growth. How can the condensate growth be driven simultaneously with a decrease in the rate of condensate diffusion? We provide insights into these seemingly contradictory observations by distinguishing between diffusion-limited and coupling-driven growth processes. Although transmembrane coupling slows down diffusion, it also locally concentrates condensates within a confined area. This confinement increases the probability of condensate coalescence and thereby promotes the growth of coupled condensates. These findings suggest that transmembrane coupling could play a role in the assembly of diverse membrane-bound structures by promoting the localization and growth of protein complexes on both membrane surfaces. This phenomenon could help to promote the assembly of transmembrane structures in diverse cellular contexts.