Nucleation of symmetric domains in the coupled leaflets of a bilayer

Abstract

We study the kinetics governing the attainment of inter-leaflet domain symmetry in a phase-separating amphiphilic bilayer. "Indirect" inter-leaflet coupling via hydrophobic mismatch can induce an instability towards a metastable pattern of locally asymmetric domains upon quenching from high temperature. This necessitates a nucleation step to form the conventional symmetric domains, which are favoured by a "direct" inter-leaflet coupling. We model the energetics for a symmetric domain to nucleate from the metastable state, and find that an interplay between hydrophobic mismatch and thickness stretching/compression causes the effective hydrophobic mismatch, and thus line tension, to depend on domain size. This leads to strong departure from classical nucleation theory. We speculate on implications for cell membrane rafts or clusters, whose size may be of similar magnitude to estimated critical radii for domain symmetry.

Undulations Drive Domain Registration from the Two Membrane Leaflets

“…However, measurements of interleaflet friction revealed the same mobility for long and short lipid molecules suggesting that there might not be permanent overhang (13). Nevertheless, the hypothesis about membrane midplane interaction is still en vogue, although, it is unclear 1) whether the liquid-disordered (L d ) domains and L o domains repel each other, or 2) whether the phenomenon is caused by attraction of the two L d domains and/or the two L o domains, or 3) what the underlying attractive or repulsive forces may generate (14,15). An alternative hypothesis with more mechanistic insight is that domain registration minimizes the line tension at the perimeter of the thicker L o phases (11): a small shift in the boundary between L d and L o domains in the two leaflets suffices to minimize the elastic deformations that arise from the hydrophobic mismatch between the two phases.…”

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.…”

“…[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.…”

“…2). Varying the inter-leaflet couplings J and B, reflecting different balances between hydrophobic mismatch and direct inter-leaflet coupling, can strongly influence kinetic outcomes, such as trapping metastable AR phases [30], or favouring them in early kinetics or in small domains [37].…”

“…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.…”