Positive effect of strong acidity on the twist of Aβ 42 fibrils and the counteraction of Aβ 42 N-terminus

Abstract pH is a crucial factor in terms of affecting the aggregation and morphology of β-Amyloid and hence a focus of study. In this study, structural and mechanical properties of a series of models (5, 6, …, 30 layer) of one-fold Aβ 42 fibrils at pH 1.5, 3.0 and 7.5, have been computed by using all-atom molecular dynamics simulations. 12, 14, and 15 layers are established to be the smallest realistic models for Aβ 42 fibrils at pH 1.5, 3.0 and 7.5, with twist angles of 0.40°, 0.34°, 0.31° respectively, disclosing the favorable effect of strong acidity on fibril twist. However, these angles are all lower than that (0.48°) determined for the truncated Aβ 17-42 fibril at pH 7.5, indicating that the disordered N-terminal depresses greatly the fibril twist and the lower pH disfavors the depression. Three commonly used indices to measure the fibril properties, namely number of H-bonds, interstrand distance and β-sheet content have imperceptible changes with the pH alternation, therefore changes in fibril twist can be taken as a probe to monitor fibril properties. By contrast, N-terminus is determined not only to inhibit the U-shaped fibril twist by hampering the stagger between β1 and β2 strands, but also to play a vital carrier role in feeling solution (i.e., pH, salt) changes. These results can help design the nextgeneration of amyloid materials for state-of-the-art bio-nano-med applications by changing the solution pH or modifying chain length.