Registered and antiregistered phase separation of mixed amphiphilic bilayers

TL;DR

This paper develops a mean-field model for coupled bilayer membranes, revealing how hydrophobic mismatch influences phase coexistence, metastability, and the kinetics of phase transitions, with implications for biological and artificial membranes.

Contribution

It introduces a new theoretical framework accounting for amphiphile structural features and hydrophobic mismatch, elucidating the competition between registration and antiregistration in bilayer phase behavior.

Findings

Equilibrium favors registered phases in phospholipid bilayers.

Metastable antiregistered phases can be kinetically stabilized.

Phase transition kinetics can involve nucleation and Ostwald's rule of stages.

Abstract

We derive a mean-field free energy for the phase behaviour of coupled bilayer leaflets, which is implicated in cellular processes and important to the design of artificial membranes. Our model accounts for amphiphile-level structural features, particularly hydrophobic mismatch, which promotes antiregistration (AR), in competition with the `direct' trans-midplane coupling usually studied, promoting registration (R). We show that the phase diagram of coupled leaflets allows multiple \textit{metastable} coexistences, then illustrate the kinetic implications with a detailed study of a bilayer of equimolar overall composition. For approximate parameters estimated to apply to phospholipids, equilibrium coexistence is typically registered, but metastable antiregistered phases can be kinetically favoured by hydrophobic mismatch. Thus a bilayer in the spinodal region can require nucleation to equilibrate, in a novel manifestation of Ostwald's `rule of stages'. Our results provide a framework for understanding disparate existing observations, elucidating a subtle competition of couplings, and a key role for phase transition kinetics in bilayer phase behaviour.