Molecular Characterization of Ionic Liquid Interactions with Lipid Membranes: Structural Dynamics, Toxicity and Biocompatibility Assessment

Abstract

This research investigates the interaction between various ionic liquids (ILs) and lipid membranes, focusing on the structural and biophysical changes induced by
ILs. Molecular dynamics simulations, along with experimental techniques such as differential scanning calorimetry (DSC), quasi-elastic neutron scattering (QENS)
and isothermal titration calorimetry (ITC), were used to assess these interactions. The results showed that the insertion of ionic liquids like [DMIM][BF4] into
lipid bilayers significantly increased the area per lipid molecule, with values observed to be around 72 Ų compared to 52 Ų for pure lipid membranes. Additionally,
the bilayer thickness decreased by approximately 1.5 nm in the presence of ILs, and membrane disorder increased, reflected by a decrease in phase transition
temperature from 44°C to 37°C. The lateral and internal motion of lipids was also enhanced, with the lateral diffusion coefficient rising by 20% upon IL
incorporation. Cytotoxicity tests indicated that ILs like [Ch][Gly] exhibited much lower toxicity levels, with a reduction in membrane damage compared to
conventional imidazolium-based ILs, showing a 40% decrease in cell viability. These findings suggest that choline amino acid-based ILs are more biocompatible
and biodegradable offering a promising alternative to traditional volatile organic solvents with minimal environmental impact.