Cholesterol-Controlled Interaction of Ionic Liquids with Model Cellular Membranes

Abstract

While ionic liquids (ILs) are considered as prospective ingredients of new antimicrobial agents, it is important to understand the adverse effects of these molecules on human cells. Since cholesterol is the essential component of a human cell membrane, in the present study, the effect of an imidazolium-based IL has been investigated on the model membrane in the presence of cholesterol. The area per sphingomyelin lipid is found to reduce in the presence of the IL, which is quantified by the area−surface pressure isotherm of the lipid monolayer formed at the air−water interface. The effect is considerably diminished in the cholesterolcontaining monolayer. Further, the IL is observed to decrease the rigidity of the cholesterol-free monolayer. Interestingly, the presence of cholesterol does not allow any change in this property of the layer at lower surface pressure. However, at a higher surface pressure, the IL increases the elasticity in the cholesterol-induced condensed phase of the lipid layer. The X-ray reflectivity measurement on a stack of cholesterol-free lipid bilayers proved the formation of IL-induced phase-separated domains in the matrix of a pure lipid phase. These domains are found to be formed by interdigitating the chains of the lipids, producing a thinner membrane. Such a phase is less intense in the cholesterol-containing membrane. All of these results indicate that the IL molecules may deform the cholesterol-free membrane of a bacterial cell, but the same may not be harmful to human beings as cholesterol could restrict the insertion in the cellular membrane of a human cell.

Role of Cholesterol in Interaction of Ionic Liquids with Model Lipid Membranes and Associated Permeability

“…ILs are reported to disorder the lipid membrane as explained in multiple recent studies. 5 , 7 , 8 , 38 Both electrostatic interactions and hydrophobic interactions play a role in the interaction between the IL and lipid films, where adsorption is primarily influenced by electrostatics, while insertion depends on the hydrophobic nature of the molecules.…”

“…However, the only requirement is that all of the components must exhibit an isotherm. The following equation is used to evaluate the Gibbs free energy from isotherm ,, normalΔ G exc = ∫ 0 π false[ A 12 − ( χ 1 A 1 + χ 2 A 2 ) false] d π Here, χ 1 and χ 2 are the mole fractions of two components used in a binary system. A 12 is the experimentally estimated mean molecular area (MMA) or the area per molecule in the monolayer of a binary system.…”

Mechanisms of Biological Effects of Ionic Liquids: From Single Cells to Multicellular Organisms

“…Notably, the presence of cholesterol in the lipid bilayers alleviated the effect of ILs . Similar results were obtained with C 10 MIm Cl . These data suggest the ability of some ILs to affect the membranes of bacterial cells (which lack cholesterol) but not mammalian cells.…”

Ionic liquids meet lipid bilayers: a state-of-the-art review

“…More recently, the role of cholesterol has been also investigated. Ghosh and co-workers looked at the effect of the imidazolium IL [dmim][Cl] on monolayers and multilayers of egg sphingomyelin lipid in the absence and presence of cholesterol (Hitaishi et al 2023 ). Overall, it turned out that the presence of cholesterol in the lipid phase reduces the effects of the IL.…”