Amphiphilic ionic liquid induced fusion of phospholipid liposomes

Abstract

We have investigated the impact of increasing concentration of imidazolium-based ionic liquids ([C_nMIM]⁺[Br]⁻) on the structural integrity of large unilamellar vesicles (LUVs) made of pure phosphatidylcholine (PC) and phosphatidylglycerol (PG) lipids. Calcein based dye leakage assays were used to monitor the permeability of LUVs in the presence of ionic liquids. As the ionic liquid concentration approaches the critical micelle value, vesicle fusion occurs resulting in unexpected quenching which is accompanied by rapid dye leakage due to the formation of transiently lived fusion-holes. Vesicle fusion is confirmed using dynamic light scattering based size measurements and fluorescence based lipid mixing assays. ¹H–¹H NOESY measurements using solid-state NMR spectroscopy were performed to obtain insights into the fusion mechanism. While POPC LUVs are more prone to membrane fusion, the overall extent of fusion is higher in POPG LUVs. Ionic liquid induced splaying of phospholipid chains is crucial for overcoming the hydration barrier between the merging bilayers.