Infrared investigation of lipid headgroups : dynamics of mixtures

Biological lipid membranes are composed of a wide variety of molecules, each with specific biological functions. The membrane is a diverse structure, and it is also dynamic and constantly fluctuating. The interplay between molecular diversity and molecular dynamics is still not understood, however a variety of techniques and tools ranging from computational simulations to microscopy have been developed and deployed to understand the movement of molecules in the lipid membrane. Infrared spectroscopy is one such tool, and can be used to measure molecular environments in condensed phases. Two-dimensional infrared spectroscopy (2D IR) combines infrared spectroscopy with precise time resolution to measure the fast fluctuations of molecules. In recent years, infrared spectroscopic techniques including 2D IR have been applied to study the dynamics of molecules in lipid membranes.

This thesis details an extension of infrared and 2D IR spectroscopy to the study of binary lipid mixtures in an effort to understand the effects of molecular diversity on lipid dynamics. In studies focused on mixtures of zwitterionic and anionic phospholipids, composition-dependent and cation dependent changes were observed in lipid dynamics. Utilization of isotope-labeled lipids further revealed the specificity of intermolecular interactions in the lipid membranes, indicating that cations selectively perturbed the environment experienced by anionic, but not cationic, lipids. Research into another set of lipid headgroups, both zwitterionic but with slightly different structures, revealed subtle patterns in hydrogen bonding and dynamics. These results are supported by atomistic molecular dynamics simulations and represent a step towards ultrafast investigations of highly heterogeneous lipid membranes.