Bicontinuous microemulsions as hosts systems for membrane peptides and proteins
Hayes, D. G.  2019.  American Oil Chemists' Society, China Section Conference, Guangzhou, China, 9-10 November, 2019.  (invited)

Membrane proteins and peptides are important biocatalysts that are responsible for many biochemical reactions and can potentially serve as therapeutical agents. Yet, their potential utility has not been realized due to difficulties in their downstream purification and finding suitable host reaction systems. We have successfully solubilized several different membrane-associated peptides and proteins into bicontinuous microemulsions (BMEs): nanoscale dispersions of oil and water at nearly equal proportions in the presence of surfactants through formation of Winsor-III microemulsion systems. We have solubilized melittin, an antimicrobial peptide possessing a broad spectrum of biological activity against microorganisms, at concentrations approaching 10 g/L in BMEs, with melittin residing in a highly folded, hence highly active, conformation, demonstrating the strong potential utility of Winsor-III systems to isolate and purify membrane proteins. Bacteriorhodopsin, a model membrane protein, readily partitions to the BME Winsor-III phase, and retains its secondary structure. The intrinsically disordered membrane peptide alpha-synuclein resides in an alpha-helical conformation, which contrast sharply with its random coil conformation in aqueous media. Small-angle neutron scattering studies, conducted using neutron contrasting techniques, show that alpha-synuclein undergoes self-aggregation inBMEs. Therefore, the behavior of alpha-synuclein in BMEs, residing near its surfactant layers, behaves quite differently than for aqueous solution, a result that may have implication in the pursuit of cures for Parkinsonís Disease.