The misfolding and aggregation of
amyloid-β (Aβ)
peptides into
amyloid fibrils in
solution and on the cell membrane has been linked to the pathogenesis of
Alzheimer's disease. Although it is well-known that the presence of different surfaces can accelerate the aggregation of Aβ
peptides into fibrils, surface-induced conformation, orientation, aggregation, and adsorption of Aβ
peptides have not been well understood at the atomic level. Here, we perform all-atom explicit-water molecular dynamics (MD) simulations to study the orientation change, conformational dynamics, surface interaction of small Aβ aggregates with different sizes (monomer to tetramer), and conformations (α-helix and β-hairpin) upon adsorption on the
graphite surface, in comparison with Aβ structures in bulk
solution. Simulation results show that hydrophobic
graphite induces the quick adsorption of Aβ
peptides regardless of their initial conformations and sizes. Upon the adsorption, Aβ prefers to adopt random structure for monomers and to remain β-rich-structure for small oligomers, but not helical structures. More importantly, due to the amphiphilic sequence of Aβ and the hydrophobic nature of
graphite, hydrophobic C-terminal residues of higher-order Aβ oligomers appear to have preferential interactions with the
graphite surface for facilitating Aβ fibril formation and fibril growth. In combination of atomic force microscopy (AFM) images and MD simulation results, a postulated mechanism is proposed to describe the structure and kinetics of Aβ aggregation from aqueous
solution to the
graphite surface, providing parallel insights into Aβ aggregation on biological cell membranes.