Abstract
β-amyloid (Aβ) peptides form self-organizing fibrils in Alzheimer's disease. The biologically active, toxic Aβ25-35 fragment of the full-length Aβ-peptide forms a stable, oriented filament network on the mica surface with an epitaxial mechanism at the timescale of seconds. While many of the structural and dynamic features of the oriented Aβ25-35 fibrils have been investigated before, the β-strand arrangement of the fibrils and their exact orientation with respect to the mica lattice remained unknown. By using high-resolution atomic force microscopy, here, we show that the Aβ25-35 fibrils are oriented along the long diagonal of the oxygen hexagon of mica. To test the structure and stability of the oriented fibrils further, we carried out molecular dynamics simulations on model β-sheets. The models included the mica surface and a single fibril motif built from β-strands. We show that a sheet with parallel β-strands binds to the mica surface with its positively charged groups, but the C-terminals of the strands orient upward. In contrast, the model with antiparallel strands preserves its parallel orientation with the surface in the molecular dynamics simulation, suggesting that this model describes the first β-sheet layer of the mica-bound Aβ25-35 fibrils well. These results pave the way toward nanotechnological construction and applications for the designed amyloid peptides.