Nucleation of symmetric domains in the coupled leaflets of a bilayer

TL;DR

This paper investigates how inter-leaflet coupling and hydrophobic mismatch influence the nucleation of symmetric domains in lipid bilayers, revealing size-dependent effects that deviate from classical nucleation theory with implications for cell membrane structures.

Contribution

It models the energetics of symmetric domain nucleation considering hydrophobic mismatch and thickness effects, highlighting size-dependent line tension and deviations from classical theory.

Findings

Hydrophobic mismatch and thickness interplay affect domain nucleation.

Line tension depends on domain size, causing non-classical nucleation behavior.

Implications for cell membrane raft sizes and stability.

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 pattern of 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.