Monitoring dynamical and structural changes at the lipid-water interface through chemical shift analysis: A xenon-129 NMR study

The accumulation of inhalational anesthetic in lipid membranes can alter their distributive properties and energetic demands. It is hypothesized that as anesthetic molecules partition into the biomembrane, changes in the lateral pressure profile ensue, indirectly altering membrane protein structure and function. Though it is well established that this dynamic process is largely controlled by interfacial properties, the actual modifications the surface tension undergoes at this boundary is not fully understood. Here, the inhalational anesthetic xenon (Xe) is used as a nonpolar, weakly binding spin probe to investigate the anesthetic-lipid bilayer interaction by gaseous NMR spectroscopy. Fundamental kinetic and thermodynamic behaviors are studied by monitoring interaction induced chemical shift changes of thermal and hyperpolarized 129Xe in various lipidic media. The nature of xenon-phospholipid interactions and Xe exchange depend on the structure of the lipid headgroups and acyl chains, the phase state of the lipid bilayer, and the heterogeneity in both vesicle size and overall distribution of lipids with external variables. The primary focus of this work is to explore the effects of temperature and composition on solvation parameters, gas adsorption properties and molecular rearrangement at the bilayer interface via 129Xe chemical shift changes.;Thermodynamic and kinetic information are extracted by monitoring the observed chemical shift with changing external variables; results are fit to a mathematical model in order to extract pertinent parameters. Partitioning behavior as related to increasing molecular stress and changing lipid morphology. Intermediate lipid phases were probed as well. Data suggests the presence of multiple binding sites as well as moderate cooperative binding. The mole fraction partition coefficient increases with temperature and behaves ideally in a single component lipid system. The presence of nonbilayer lipids has an opposite effect on the partitioning parameters. What's more, evidence suggests the addition of Xe promotes the formation of highly curved structures at elevated temperatures and pressures. Anodic Aluminum Oxide (AAO) substrates are utilized to stabilize bilayers in the magnetic field, facilitating the study of Xe diffusivity between phases using 2D-exchange NMR methods. Results are discussed in context of anesthetic action and the lateral pressure profile.