Amphiphilic Ionic Liquid Induced Fusion of Phospholipid Liposomes

Membrane fusion is a key biological phenomenon with potential applications in biotechnology. In this work, we provide biophysical and structural evidence that liposomes composed of POPC/POPG phospholipids undergo fusion in the presence of ionic liquids containing 1-alkyl-3-methyl-imidazolium cations. The fusion phenomenon is confirmed using dynamic light scattering based size measurements, and Fluorescence based dye leakage and lipid mixing assays. 1H-1H NOESY measurements using solid-state NMR spectroscopy were performed to obtain insights into fusion mechanism. It is found that ionic liquid induced splaying of phospholipid chains is crucial for overcoming the hydration barrier between the merging bilayers. Also, transiently lived fusion-holes are formed at the initial stages of bilayer mixing resulting in a leaky fusion phenomenon. Although considered as “green” alternatives to conventional solvents, ionic liquids can exhibit cytotoxicity by altering the structural integrity of cellular membrane. Our study provides mechanistic details of the evolution of phospholipid membrane structure resulting in membrane fusion when subjected to increasing ionic liquid concentrations. We believe that findings of this study will further our understanding of ionic liquids induced cytotoxicity and non-protein assisted membrane fusion.