Amyloid-β peptides time-dependent structural modifications: AFM and voltammetric characterization.

Abstract The human amyloid beta (Aβ) peptides, Aβ 1-40 and Aβ 1-42 , structural modifications, from soluble monomers to fully formed fibrils through intermediate structures, were investigated, and the results were compared with those obtained for the inverse Aβ 40-1 and Aβ 42-1 , mutant Aβ 1-40 Phe 10 and Aβ 1-40 Nle 35 , and rat Aβ 1-40 Rat peptide sequences. The aggregation was followed at a slow rate, in chloride free media and room temperature, and revealed to be a sequence-structure process, dependent on the physicochemical properties of each Aβ peptide isoforms, and occurring at different rates and by different pathways. The fibrilization process was investigated by atomic force microscopy (AFM), via changes in the adsorption morphology from: (i) initially random coiled structures of ∼0.6 nm height, corresponding to the Aβ peptide monomers in random coil or in α-helix conformations, to (ii) aggregates and protofibrils of 1.5–6.0 nm height and (iii) two types of fibrils, corresponding to the Aβ peptide in a β-sheet configuration. The reactivity of the carbon electrode surface was considered. The hydrophobic surface induced rapid changes of the Aβ peptide conformations, and differences between the adsorbed fibrils, formed at the carbon surface (beaded, thin, 2.0 nm height), were detected. Differential pulse voltammetry showed that, according to their primary structure, the Aβ peptides undergo oxidation in one or two steps, the first step corresponding to the tyrosine amino acids oxidation, and the second one to the histidine and methionine amino acids oxidation. The fibrilization process was electrochemically detected via the decrease of the Aβ peptide oxidation peak currents that occurred in a time dependent manner.