Divide and conquer: How phase separation contributes to lateral transport and organization of membrane proteins and lipids

[Display omitted] •Lipid demixing can redistribute lipids and proteins into distinct membrane domains.•Curvature influences lipid composition and protein spatial distribution in both model and biological systems.•Steric, electric, and hydrodynamic forces can redistribute lipids and proteins laterally within membranes. Biological membranes are fluid, dynamic and heterogeneous, with the dual tasks of defining cell compartments and facilitating communication between them. Within membranes, lipid phase separation can alter local composition, dynamics, and allosteric regulation of membrane proteins. The interplay between lipid–lipid, lipid–protein and protein–protein interactions gives flexibility to membrane lateral organization. In this review we examine how lipid phase separation impacts lateral transport of lipids and proteins within membranes. First, we discuss the role of liquid–liquid coexistence in the organization of model biomembranes, and how such demixing can redistribute lipids and proteins into different regions. Next, the role of curvature in membrane patterning via its influence on lipid composition and protein spatial distribution in both model and biological systems is examined. Then, we discuss how critical fluctuations can organize membrane proteins. Finally, we review how external forces can be used to control the organization of lipids and proteins within biomembranes; with examples covering how ATP driven protein adsorption, electrophoresis, and hydrodynamic flow can transport and redistribute lipids and proteins laterally within membranes.