Structural Determination of Membrane Mimics Using Small-angle X-ray and Neutron Scattering

Oliver, Ryan, Chemistry - Graduate School of Arts and Sciences, University of Virginia
Columbus, Linda, Department of Chemistry, University of Virginia

The challenge of finding a suitable membrane mimic that produces a stable and functionally active membrane protein is one of the primary obstacles faced in membrane protein investigations. Not only is there a lack of understanding about the properties of the surrounding environment that produce such a stable complex, but many physical properties, such as size and shape, of the membrane mimics themselves remain uncharacterized. This dissertation presents the determination of such physical properties from small-angle scattering detergent-based membrane mimics to serve as a baseline for investigating how certain factors of the membrane mimic might influence membrane protein stability. First, the dependence of micelle size and shape on detergent monomer structure, such as head group chemistry and alkyl chain length, was determined using systematic variations in detergent structures and measuring properties of the resulting micelles formed. Next, detergent mixtures were investigated to determine the dependence of mixed micelle properties on detergent composition. Finally, aggregate structures of lipid-detergent mixtures expected to form bicelles were characterized in the detergent-rich regime. Contrast variation experiments performed on aggregates formed by these mixtures are expected to reveal internal organization and distribution of lipid and detergent molecules between the bicelle core and rim regions.

PHD (Doctor of Philosophy)
membrane protein, detergent, micelle, bicelle, SAXS, SANS
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