Kinetics of symmetry and asymmetry in a phase-separating bilayer membrane.

We simulate a phase-separating bilayer in which the leaflets experience a direct coupling favoring local compositional symmetry ("registered" bilayer phases), and an indirect coupling due to hydrophobic mismatch that favors strong local asymmetry ("antiregistered" bilayer phases). For wide ranges of overall leaflet compositions, multiple competing states are possible. For estimated physical parameters, a quenched bilayer may first evolve toward a metastable state more asymmetric than if the leaflets were uncorrelated; subsequently, it must nucleate to reach its equilibrium, more symmetric, state. These phase-transition kinetics exhibit characteristic signatures through which fundamental and opposing interleaflet interactions may be probed. We emphasize how bilayer phase diagrams with a separate axis for each leaflet can account for overall and local symmetry or asymmetry, and capture a range of observations in the experiment and simulation literature.