Decoding the Microscopic Effects of Biocompatible Ionic Liquids on Model Phospholipid Membrane

Abstract

Ionic liquids (ILs) are increasingly explored in pharmaceutical and therapeutic applications because of their roles in drug delivery and biomolecular stabilization. As cell membranes serve as the primary protective barrier of the cellular environment, decoding the effects of ILs on membrane properties is of important scientific and biomedical interest. In this work, attempts have been made to investigate the microscopic effects of three biocompatible ILs with varying degrees of hydrophilic characters, namely, cholinium nitrate [CHL][NO3], ethylammonium nitrate [ETA][NO3], and ethanolammonium nitrate [ETAH][NO3], on the dipalmitoylphosphatidylcholine (DPPC) lipid bilayer using atomistic molecular dynamics (MD) simulations. The calculations revealed that the presence of the ILs induces greater disorder in the DPPC lipid bilayer, and the effect becomes stronger with an increase in the hydrophilicity of the IL components. Hydrophilic IL cations are found to exhibit a greater propensity to form hydrogen bonds with the lipid headgroups, thereby strengthening their interaction with the lipid molecules. This, in turn, causes enhanced disorder in the lipid bilayer. Importantly, a deeper analysis demonstrated that IL-induced bilayer disordering leads to increasing water permeation across the membrane, although the fundamental permeation mechanism remains largely unaltered. We believe that such in-depth analyses can help design safe and effective ILs for various biomedical applications.