Abstract
The β-amyloid peptide (Aβ) is a 39-43 amino acid peptide, fragment-derived from proteolytic cleavage of the large amyloid precursor protein (APP). The monomers or oligomers of Aβ are soluble, but at higher concentrations Aβ will self-assemble into fibrils. The fibrillar aggregates of Aβ are associated to Alzheimer’s disease. The interaction between Aβ monomer and membrane is a key factor to the Alzheimer’s disease. Amphiphilic molecules such as surfactants were known to either promote or reduce the fibril aggregation of Aβ. In this study, we used scattering methods and other techniques to investigate the interaction of Aβ with surfactants and lipid membranes. The structure and structural evolution of the complexes formed by β-Amyloid (Aβ) 1-40 peptides with sodium dodecyl sulfate (SDS) surfactants of a critical micelle concentration (CMC) of 8 mM were investigated by small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS) at below the CMC and above the CMC of SDS. With the scattering contrast varied by the deuteration of the 6 mM SDS added in the aqueous solutions of 0.115 mM Aβ peptides, the measured SANS data indicate that the typical fibril aggregation of the Aβ peptides is suppressed by the SDS monomers via the formation of short rod-like Aβ peptide/SDS complexes. The rod-like complexes, characterized by a rod radius of 13 Å, a rod length of 49 Å, and aggregation numbers of two Aβ peptides and sixty SDS monomers, further form fractal-like clusters of a fractal dimension of 1.6 and a correlation length of 430 Å. For the solution of 0.115 mM Aβ peptides added with 20 mM SDS (with SDS micelles), the time-dependent SAXS data measured indicate that the Aβ peptides adsorbed to the surfaces of the SDS micelles, and formed peptide/SDS complexes of a core-shell structure based on the preexisting SDS micelles. Using an ellipsoid-like model of a core-shell structure, we have extracted respectively the semi-major and semi-minor axes of 22 Å and 16 Å of the ellipsoidal core and a shell thickness of ~4 Å for the peptide/SDS micelle complexes. With circular dichroism (CD), we have also shown that either 6 mM SDS monomers or 20 mM SDS with micelles can maintain the secondary structures of the Aβ peptides largely in an a-helix structure. As for the interaction of the Aβ with lipid membrane, the effect of the insertion of Aβ in the 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) multibilayers supported on silicon wafer was studied by using grazing-incident small-angle X-ray scattering at different bilayer hydration levels (changing the relatively humidity) at the weight ratio of peptide to lipid weight ratio of 1 to 10. It was found that the amyloid peptides form clusters in the bilayer and possess in-plane correlation. From analyzing the diffuse scattering around the Bragg peak in the lateral direction, the amyloid peptides are found to form clusters in the bilayer with a radius of about 9 nm. As the relative humidity exceeds about 94 %, the Aβ clusters seem to develop ordered structure with a spacing of about 300 Å. We have also investigated the amyloid peptide fibrils/monomers interacting with DPPC vesicles. In the gel to ripple transition of the lipid bilayers, we found that in the presence of amyloid fibrils the riple phase of lipid bilayers was suppressed. In the presence of amyloid monomers, the lipid multilamellar liposomes were turned into structures similar to unilamellar vesicles or unbinding multilamellar membranes.