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

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 lipid domain area fraction, total lipid domain perimeter over time and total number of lipid domains over time for two different membrane compositions (DOPC:DPPC with a 2:1 M ratio with 20% Chol and DOPC:DPPC with a 3:1 M 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.

Keywords: Computational modeling; Fluorescence microscopy; Liposomes; Membrane phase separation; Multicomponent membranes; Phase-field model.