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Cholesterol-Controlled Interaction of Ionic Liquids with Model Cellular Membranes

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LANGMUIR
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AMER CHEMICAL SOC
DOI: 10.1021/acs.langmuir.3c00883

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The impact of an imidazolium-based ionic liquid (IL) on model cell membranes with and without cholesterol has been studied. The IL reduces the area of the cholesterol-free membrane and increases the elasticity of the cholesterol-containing membrane. X-ray reflectivity measurements confirm the formation of IL-induced phase-separated domains in the pure lipid phase. These results suggest that IL may deform bacterial cell membranes without cholesterol, but may not be harmful to human cell membranes due to the presence of cholesterol.
While ionic liquids (ILs) are considered as prospectiveingredientsof new antimicrobial agents, it is important to understand the adverseeffects of these molecules on human cells. Since cholesterol is theessential component of a human cell membrane, in the present study,the effect of an imidazolium-based IL has been investigated on themodel membrane in the presence of cholesterol. The area per sphingomyelinlipid is found to reduce in the presence of the IL, which is quantifiedby the area-surface pressure isotherm of the lipid monolayerformed at the air-water interface. The effect is considerablydiminished in the cholesterol-containing monolayer. Further, the ILis observed to decrease the rigidity of the cholesterol-free monolayer.Interestingly, the presence of cholesterol does not allow any changein this property of the layer at lower surface pressure. However,at a higher surface pressure, the IL increases the elasticity in thecholesterol-induced condensed phase of the lipid layer. The X-rayreflectivity measurement on a stack of cholesterol-free lipid bilayersproved the formation of IL-induced phase-separated domains in thematrix of a pure lipid phase. These domains are found to be formedby 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 thecholesterol-free membrane of a bacterial cell, but the same may notbe harmful to human beings as cholesterol could restrict the insertionin the cellular membrane of a human cell.

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