CoQ10 selective miscibility and penetration into lipid monolayers with lower lateral packing density

Abstract

CoQ₁₀ is ubiquitously present in eukaryotic cells. It acts as electron carrier in the electron transport chain of the inner membrane of the mitochondria to facilitate aerobic cellular respiration. A highly stable lipid nanodispersion formulation containing CoQ₁₀ (BPM31510) is currently in clinical investigation for treatment of cancer. This study was designed to determine whether biophysical interactions between CoQ₁₀ and lipid, in part, explain the observed stability and cellular accumulation of CoQ₁₀ in cells and tissues. A lipid monolayer at the air-water interface was used as an experimental membrane model to measure CoQ₁₀ penetration and solubility. Lipid monolayers with varying proportions of CoQ₁₀ were laterally compressed to measure CoQ₁₀ miscibility and lateral organization. Additionally, lipid monolayers with varying lateral packing densities were spread at the air-water interface and CoQ₁₀ was injected in proximity to measure its rate of penetration. Our results demonstrate that CoQ₁₀ selectively penetrates into lipid monolayers with a lower lateral packing density, and is excluded by monolayers of higher packing densities. Data also indicates that CoQ₁₀-lipid mixing is non-ideal. CoQ₁₀ presence in lipid monolayers is biphasic, with one phase occupying the interstitial space between the DMPC lipids, and the other phase is present as pure CoQ₁₀ domains. This work provides further insight into mechanism of action of CoQ₁₀ based formulations that can significantly increase intracellular CoQ₁₀ concentration to show pleotropic effects on cellular functions.

Keywords: CoQ(10); Lipid; Membrane.