Lipid domain coarsening and fluidity in multicomponent lipid vesicles: A continuum based model and its experimental validation

Abstract

Liposomes that achieve a heterogeneous and spatially organized surface through phase separation have been recognized to be a promising platform for delivery purposes. However, their design and optimization through experimentation can be expensive and time-consuming. To assist with the design and reduce the associated cost, we propose a computational platform for modeling membrane coarsening dynamics based on the principles of continuum mechanics and thermodynamics. This model couples phase separation to lateral flow and accounts for different membrane fluidity within the different phases, which is known to affect the coarsening dynamics on lipid membranes. The simulation results are in agreement with the experimental data in terms of liquid ordered domains area fraction, total domains perimeter over time, and total number of domains over time for two different membrane compositions (DOPC:DPPC with a 1:1 M ratio with 15% Chol and DOPC:DPPC with a 1:2 M ratio with 25% Chol) that yield opposite and nearly inverse phase behavior. This quantitative validation shows that the developed platform can be a valuable tool in complementing experimental practice.

Keywords: Computational modeling; Fluorescence microscopy; Liposomes; Membrane fluidity; Membrane phase separation; Multicomponent membranes.