Partitioning of a Hybrid Lipid in Domains of Saturated and Unsaturated Lipids in a Model Cellular Membrane

The cellular membranes are composed of hundreds of components such as lipids, proteins, and sterols that are chemically and physically distinct from each other. The lipid−lipid and lipid−protein interactions form domains in this membrane, which play vital roles in membrane physiology. The hybrid lipids (HLs) with one saturated and one unsaturated chain can control the shape and size of these domains, ensuring the thermodynamic stability of a membrane. In this study, the thermodynamics of mixing of a HL and its structural effects on the phase separated domains in a model membrane composed of a saturated and an unsaturated lipid have been investigated. The HL is observed to mix into an unsaturated lipid reducing the Gibbs free energy, whereas the mixing is unfavorable in a saturated lipid. The presence of an HL in an unsaturated lipid tends to increase its area fraction, which is reflected in the enhanced correlation length across the bilayers in a multilayered sample. There is a feeble effect on the domain structure of the saturated lipid due to the presence of the HLs at the phase boundary. This study concludes that the HLs preferentially participate in the unsaturated lipid regions compared to that of a saturated lipid

How 1,n-Bis(3-alkylimidazolium-1-yl) Alkane Interacts with the Phospholipid Membrane and Impacts the Toxicity of Dicationic Ionic Liquids

Ionic liquids based on doubly charged cations, often termed dicationic ionic liquids (DILs), offer robust physicochemical properties and low toxicity than conventional monocationic ionic liquids. In this design-based study, we used solid-state NMR spectroscopy to provide the interaction mechanism of two DILs, 1,n-bis(3-alkylimidazolium-1-yl) alkane dibromide ([C2n(C7–nIM)2]2+·2Br–, n = 1, 6), with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (POPG) phospholipid membranes, to explain the low toxicity of DILs toward HeLa, Escherichia coli, Bacillus subtilis, and Saccharomyces cerevisiae cell lines. Dications with a short linker and long terminal chains cause substantial perturbation to the bilayer structure, making them more membrane permeabilizing, as shown by fluorescence-based dye leakage assays. The structural perturbation is even higher than [C12(MIM)]+ monocations, which carry a single 12-carbon long chain and exhibit a much higher membrane affinity, permeability, and cytotoxicity. These structural details are a crucial contribution to the design strategies aimed at harnessing the biological activity of ionic liquids