Hybrid molecule enables liquid-liquid phase separation in a minimal lipid membrane with only two components

Liquid-liquid phase separation occurs in a variety of lipid membranes, both biological and synthetic. Except in extraordinary circumstances, at least three lipid components are needed: a phospholipid with ordered chains, a phospholipid with disordered chains, and a sterol. This fact is puzzling, as two components are sufficient from a theoretical standpoint, as well as for liquid-liquid phase separation in lipid monolayers. This hinders understanding of the physics of such transitions in lipid bilayers, as the extra component results in more complicated thermodynamics.

In search of a two-component bilayer displaying liquid-liquid phase separation, we test mixtures in which the sterol and the ordered phospholipid of a phase-separating mixture are replaced with a single, joined sterol-lipid molecule. We find system-scale, reversible, liquid-liquid phase separation in a bilayer with only two components: a sterol-lipid molecule (PChemsPC) and a phospholipid with disordered chains (diPhyPC). This is a truly minimal model system for liquid-liquid phase separation in a bilayer membrane. We construct a miscibility phase diagram for this membrane, from which it is straightforward to determine tie-lines, and thus the composition of each phase.