DETERGENT MICELLE STRUCTURE AND MICELLE-MICELLE INTERACTIONS DETERMINED BY SMALL-ANGLE NEUTRON-SCATTERING UNDER SOLUTION CONDITIONS USED FOR MEMBRANE-PROTEIN CRYSTALLIZATION

We have characterized micelle structure and intermicelle interaction f or the detergents lauryldimethylamine N-oxide, LDAO, and n-octyl-beta- D-glucoside, OG, under conditions used for protein crystallization usi ng SANS. We found that LDAO and OG micelles differ significantly in si ze, sensitivity to heptanetriol, and nature of intermicelle interactio ns. Our results suggest that successful crystallization methods can be rationalized in terms of an optimization of micelle size, number dens ity, flexibility of micelle radius of curvature, and suppression of in termicelle interactions. LDAO and OG micelles were found to differ sig nificantly in size and shape. The LDAO micelle was found to be best fi t as an ellipsoid with semiaxes of 30.6 and 19.4 Angstrom, while the O G micelle was found to be spherical with a radius of 22.9 Angstrom. Th e addition of heptanetriol to pure LDAO resulted in the formation of s maller, spherical, mixed micelles with radii in the range 17-21 Angstr om, depending upon conditions. The results suggest that both micelle s ize and curvature restrictions may contribute to the incompatibility o f LDAO for protein crystallization in the absence of additional amphip hiles. The mixed OG-heptanetriol micelle was found to be significantly smaller than that with LDAO, having radii in the range 15-18 Angstrom , depending upon conditions, and exhibited a greater number density in crease. Evidence was found for interaction between OG and polyethylene glycol, PEG, that prevents micelle aggregation at high ionic strength and likely contributes to the particular success of PEG as a protein precipitant when OG is used as the solubilizing detergent. These measu rements suggest that the chemical constituents in membrane protein cry stallization can be manipulated to optimize micelle size, number densi ty, and interparticle interactions.