Ionic liquids (ILs) are important for their antimicrobial activity and are found to be toxic to some microorganisms. To shed light on the mechanism of their activities, the interaction of an imidazolium-based IL 1-butyl-3-methylimidazolium tetrfluoroborate ([BMIM][BF]) with E. coli bacteria and cell-membrane-mimicking lipid mono- and bilayers has been studied. The survival of the bacteria and corresponding growth inhibition are observed to be functions of the concentration of the IL. The IL alters the pressure-area isotherm of the monolayer formed at an air-water interface by the 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid. The in-plane elasticity of the lipid layer is reduced as a consequence of the insertion of this IL. The X-ray reflectivity study from a polymer-supported lipid bilayer shows strong perturbation in the self-assembled structure of the bilayer due to the interaction. As a consequence, there is a considerable decrease in bilayer thickness and a corresponding increase in electron density. These results, however, depend on the chain configurations of the lipid molecules.

The interaction of phospholipids with the peripheral membrane proteins like spectrin is important not only to understand the various physiological functions of cells, but also to gain insight into the mechanism involved in the self-assembly of polymer-like long chain molecules at the soft surfaces and interfaces. The lipid head-group specificity of adsorption of spectrin to supported phopsholipid bilayer model membranes has been investigated using the X-ray reflectivity (XRR) technique. Model lipid bilayers composed of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) head groups have been prepared on a soft polymer cushion and the XRR measurements have been carried out from the bilayers immersed in a water bath using high-energy synchrotron X-rays. Our results suggest that in PC-based membranes the spectrin chains form a uniform layer on top of the bilayer with their chains lying on the membrane surface, while in PE-based membranes with relatively smaller head groups, the spectrin chains are attached only through a few possible binding sites with the rest of the part projected out of the membrane surface. In addition, the reflectivity profiles reveal the penetration of spectrin polypeptide chains through the PE bilayer in its fluid phase. Pressure-area isotherm measurements on Langmuir monolayers also support similar observations on the adsorption of spectrin molecules to the membranes composed of PC and PE. The observed results were explained using a qualitative model based on the ion-mediated protein interaction in the PC-based membrane.

Drug design and targeted delivery in cells serve as a flourishing area not only for scientific inquiry, owing to numerous clinical applications, but also for understanding cell interaction with exogenous materials. The membrane localization of heme and its analog hemin, one of the most biologically relevant planar organic molecule, is very important to understand the molecular mechanism of intercalation and adsorption of this cytotoxic molecule after its dissociation from proteins such as hemoglobin. Herein, we investigate the differential behavior of hemin on the soft membrane surfaces of phospholipids by synchrotron-based X-ray scattering techniques, Langmuir monolayer measurements, and molecular dynamics simulation. A continuous hemin uptake from the subphase and intercalation into and/or adsorption on to the membrane surface have been witnessed in a strong membrane surface packing-specific manner. Competitive interactions between hemin-membrane and hemin-hemin are proposed to be responsible for the critical hemin concentration. Up to the limit, a continuous hemin uptake is possible and beyond that the hemin-hemin interaction dominates, effectively reducing the hemin intercalation into the membrane. This structural model of the hemin-uptake process can be generalized to understand the localization and transport across membranes and also for the development and design of new drugs.

Lateral and out-of-plane organization of cholesterol and its effect on regulating the physicochemical properties of zwitterionic phospholipid model membranes have been investigated by a pressure-area isotherm study from the Langmuir monolayer, atomic force microscopy (AFM), and X-ray reflectivity (XRR) measurements from supported binary monolayer films. The systematic isotherm studies on the Langmuir monolayer of phospholipids and the subsequent extraction of excess Gibbs free energy (ΔG) revealed the mechanism of cholesterol interaction and the molecular cooperativeness for different arrangements in the phospholipid model membranes. We have found a critical cholesterol molar concentration (χ) up to which the lipid-cholesterol miscibility gradually increases and then further increase in the concentration leads to an inhomogeneous structure formation similar to raft structures. The thickening in the lipid acyl chain and the subsequent lowering of the lipid head group thickness up to χ are also evident from the XRR study. Beyond χ, large-sized domains are observed in the AFM images from the deposited monolayer. χ has also been observed to depend on the phase of the monolayer, in particular, ∼25 molar % in the gel phase and ∼40 molar % in the fluid phase, wherein a regular distribution has been found with the highest separation between the cholesterol molecules. The extracted isothermal compressibility coefficient (C) and ΔG from the monolayer isotherms indicate that the molecular arrangement at χ are the most stable configurations of the monolayer. Our study provides direct evidence into cholesterol-induced evolution in phase behavior and the consequent model on the structure at different phases in the phospholipid Langmuir monolayers.

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