Amphiphilic Ionic Liquid-Induced Membrane Permeabilization: Binding Is Not Enough

The interaction of amphiphilic ionic liquids containing an 1-alkyl-3-methylimidazolium cation ([C₁₂MIM]⁺), which shows acute cytotoxicity toward marine and bacterial life, with zwitterionic 1-palmitoyl-2-oleoyl- sn-glycero-3-phospho-choline (POPC) and anionic 1-palmitoyl-2-oleoyl- sn-glycero-3-phospho- rac-glycerol (POPG) membranes was investigated. Biophysical parameters of this interaction were quantified by fluorescence spectroscopy, isothermal titration calorimeter, and solution-state NMR measurements. [C₁₂MIM]⁺ inserts into the membrane and induces vesicle leakage at relatively low concentration (<1 mM). Zwitterionic POPC membranes are more leakage-prone, but the binding of [C₁₂MIM]⁺ cations is stronger to anionic POPG membranes. A higher rate of exchange of membrane-bound [C₁₂MIM]⁺ is suspected to play a key role in membrane leakage. Furthermore, solid-state NMR spectroscopy was employed to determine the location of [C₁₂MIM]⁺ in lipid membranes and its impact on the structure and dynamics of the bilayer. The study provides a molecular understanding of the membrane permeabilizing effect of the [C₁₂MIM]⁺ mediated by its detergent-like structure.