Experimental validation of a phase-field model to predict coarsening dynamics of lipid domains in multicomponent membranes

TL;DR

This study validates a computational phase-field model that accurately predicts lipid domain coarsening in membranes, aiding the design of organized liposomes and reducing experimental costs.

Contribution

The paper introduces a thermodynamically informed surface Cahn-Hilliard phase-field model that quantitatively matches experimental data on membrane domain dynamics.

Findings

Model accurately predicts raft area fraction over time

Excellent agreement between simulations and experiments on raft perimeter

Model reduces experimental effort in liposome design

Abstract

Membrane phase-separation is a mechanism that biological membranes often use to locally concentrate specific lipid species in order to organize diverse membrane processes. Phase separation has also been explored as a tool for the design of liposomes with heterogeneous and spatially organized surfaces. These "patchy" liposomes are promising platforms for delivery purposes, however their design and optimization through experimentation can be expensive and time-consuming. We developed a computationally efficient method based on the surface Cahn-Hilliard phase-field model to complement experimental investigations in the design of patchy liposomes. The method relies on thermodynamic considerations to set the initial state for numerical simulations. We show that our computational approach delivers not only qualitative pictures, but also accurate quantitative information about the dynamics of the membrane organization. In particular, the computational and experimental results are in excellent agreement in terms of raft area fraction, total raft perimeter over time and total number of rafts over time for two different membrane compositions (DOPC:DPPC with a 2:1 molar ratio with 20% Chol and DOPC:DPPC with a 3:1 molar ratio with 20% Chol). Thus, the computational phase-field model informed by experiments has a considerable potential to assist in the design of liposomes with spatially organized surfaces, thereby containing the cost and time required by the design process.