NMR and lateral diffusion in membranes

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Lateral diffusion refers to the random movement of proteins, lipids and other molecules within the plane of the biomembranes found in and surrounding living cells.  Many cellular physiological processes are controlled by lateral diffusion.  Current methods for measuring lateral diffusion are cumbersome, time-consuming, and potentially perturbing.  In this proposal we present novel techniques for rapidly measuring lateral diffusion in membranes using nuclear magnetic resonance (NMR) spectroscopy, a non-perturbing technique.  These are adapted from established NMR diffusion methods, but are re-designed to accommodate the unique difficulties of membranes.  In addition, we describe a novel model membrane system especially tailored for the study of lateral diffusion via NMR.  These new NMR lateral diffusion methods and new model membrane system will be applied in measuring lateral diffusion of important membrane-seeking fluorinated drugs, as well as carotenoids, a class of membrane-bound molecules with uniquely useful optical properties.  Additionally, lateral diffusion will be measured within domains induced by oligonucleotides of the type used for gene therapy applications, and within lipid rafts, a recently identified membrane structure of fundamental functional importance but as yet poorly understood from a structural / dynamics standpoint.