Role of Cholesterol in Interaction of Ionic Liquids with Model Lipid Membranes and Associated Permeability

In this work, we explored how the amount of cholesterol in the lipid membrane composed of phosphatidylcholine (POPC) or phosphatidylglycerol (POPG) affects the interaction with 1-dodecyl-3-methylimidazolium bromide ([C₁₂MIM]⁺Br^-) ionic liquids using various biophysical techniques. On interacting with the membrane, [C₁₂MIM]⁺Br^- leads to enhanced membrane permeability and induces membrane fusion, leading to an increase in vesicle size. The ²H-based solid-state NMR investigations of cholesterol-containing lipid membranes reveal that [C₁₂MIM]⁺Br^- decreases the lipid chain order parameters and counteracts the lipid condensation effect of cholesterol to some extent. Therefore, as the amount of cholesterol in the membrane increases, the membrane effect of [C₁₂MIM]⁺Br^- decreases. The effect of [C₁₂MIM]⁺Br^- on the membrane properties is more pronounced for POPC compared to that of POPG membranes. This suggests a dependence of these effects on the electrostatic interactions, indicating that the influence of [C₁₂MIM]⁺Br^- varies based on the lipid composition. The findings suggest that the presence of cholesterol can modulate the effect of [C₁₂MIM]⁺Br^- on membrane properties, with variations observed between POPC and POPG membranes, highlighting the importance of lipid composition. In short, this study provides insights into the intricate interplay between cholesterol, the lipid membrane, and the ionic liquid [C₁₂MIM]⁺Br^-.