Solid state NMR techniques will be employed to examine the dynamic structure of lipids and peptides in lipid bilayers. The experiments can be divided into six categories: (1) Using the anisotropy of the spin lattice relaxation, which we have recently observed in the L alpha phase of a three lipid species, together with lineshape simulations, it is possible to specify the dynamic structure of lipids in a bilayer. We intend to examine L alpha phase PC's, PE's, SM's, PS's and glycolipids with this technique. Oriented samples will be employed to assess the effects of diffusional averaging of T1, and a theory of T1 for anisotropic motion will be developed. (2) We have examined three lipid/cholesterol (CHOL) mixtures with NMR. Trends appear to be emerging, indicating common interactions between lipids and the sterol. We therefore plan to examine sphingomyelin (SM)/CHOL and phosphatidylserine (PS)/CHOL mixtures since these are the two remaining lipid classes whose interaction with the sterol have not been investigated. (3) The dynamic structure of defined binary and ternary lipid mixtures which mimic those found in biological membranes will be examined. (4) The changes in the phase behavior and dynamic structure induced by ions such as Ca2+, Li+, and Mg2+ in charged lipid membranes like PS - isothermal transitions - will be studied with 2H and 13C magic angle spinning NMR. (5) Diffusion of peptides in bilayers will be studied by isotopically labelling the peptide and observing the temperature dependence of motionally averaged powder spectra. (6) Two new solid state NMR techniques, rotational resonance and REDOR which can be used to measure homonuclear and heteronuclear distances up to ~5A, will be employed to determine the structure of signal peptides and peptide antibiotics in bilayers.

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National Institute of General Medical Sciences (NIGMS)
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