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

Abstract

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.

Effects of passive phospholipid flip-flop and asymmetric external fields on bilayer phase equilibria

“…1A, we use a semi-microscopic lattice model of coupled leaflets [1,2,30]. We emphasise, however, that a similar form of landscape also arises from a fully phenomenological approach [4,[25][26][27], and most of our findings here follow from very general considerations common to either case.…”

“…An exhaustive phase diagram including further regions of metastable coexistence may be found in Ref. [2]. C) "Post flip-flop" phase diagram at late times.…”

“…[4,[25][26][27]. We describe our specific implementation of this approach [1,2,30] and the parameters used in the rest of the paper. In Section III we use this approach to develop a theory to describe the effects of flip-flop and external fields on phase behaviour.…”

“…We use a Monte Carlo simulation protocol that resembles spin-exchange dynamics on each leaflet and is as given in [2,30], with the addition of five attempted leaflet-exchange (flip-flop) moves per Monte Carlo…”

“…In such cases the question of whether domains in one leaflet "induce them in the other" is more accurately phrased as whether or not the direct inter-leaflet coupling is sufficient that the R-AR tie-lines deviate from vertical or horizontal. If an R-AR tie-line is flat, the composition and 'phase' of one leaflet will be uniform between both the R and the AR phases (although the other leaflet changes its composition) [2,30]. Similarly, the question of whether one leaflet's composition "suppresses domain formation in the other" is the question of whether some given φ t = φ b takes the bilayer outside any coexistence regions of the leafletleaflet phase diagram, so that both leaflets then remain uniform.…”