Aggregation structure of Alzheimer amyloid-β(1–40) peptide with sodium dodecyl sulfate as revealed by small-angle X-ray and neutron scattering

Abstract

Using small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS) with contrast variation, we have studied the complex aggregation of Alzheimer amyloid-β(1–40) (Aβ) peptides with sodium dodecyl sulfate (SDS). With the addition of 0.115 mM Aβ peptide into an aqueous solution containing 6 mM SDS, time-dependent SAXS indicates the formation of a globular SDS–Aβ complex with a core–shell structure. The emergence of the complex aggregates, however, lags significantly behind the fast transition of the secondary structure of Aβ peptides from random coil to α-helical structure observed by circular dichroism (CD). With scattering contrast varied by SDS and deuterated SDS, SANS results reveal the coexistence of Aβ aggregates and the SDS–Aβ complex, which together form clusters of a mass fractal structure. Based on the changes of the zero-angle scattering intensity with the contrast variation, a molecular association ratio, ∼30 : 1, of SDS to Aβ is extracted for the globular complex micelle. With a concentration (20 mM) above the critical micelle concentration (CMC) of SDS, time-dependent SAXS and CD reveal a better synchronization between the formation of the SDS–Aβ complex and the changes in Aβ secondary structure. Using an ellipsoid model with a core–shell structure in the SAXS data analysis, we have extracted detailed structural information of the prolate, core-shelled SDS–Aβ complex, having size and shape resembling pure SDS micelles. The significantly larger electron density of the shell of the complex, as compared to that of pure SDS micelles, suggests that the hydrophilic parts of Aβ peptides can situate well with the sulfate headgroups of SDS in the shell region. Delicate differences in the micellar structure and the formation pathway of the two types of SDS–Aβ complexes, respectively formed in aqueous solutions containing SDS concentrations below and above its CMC, are discussed in terms of the dissimilar association efficiencies of Aβ peptides with SDS monomers and SDS micelles. The morphology, association ratio, and clustering behavior of the SDS–Aβ complex obtained in this study may have implications in interpreting the related spectroscopy and SDS–PAGE results of the protein.