Length-dependent β-sheet growth mechanisms of polyalanine peptides in water and on hydrophobic surfaces

Fibrillar assemblies by peptides are becoming one of the most promising nanomaterials due to their exceptional properties. The self-assembly of peptides into β sheets is a critical step in the fibrillization pathway. We investigated the length-dependent β-sheet growth mechanisms of polyalanine [poly(A)] peptides consisting of 6 to 24 alanines (A6 to A24) in water and on the hydrophobic surface, respectively, by molecular dynamics simulations. β-sheet growth behavior in water fits negative exponential growth model, showing that β-sheet growth rate decays exponentially with time. Meanwhile, increasing chain length leads to an accelerated decay of the β-sheet growth rate. By contrast, β-sheet growth on the surface from A6 to A18 occurs in two consecutive stages, both of which fit linear growth models. β-sheet growth rate in the first stage increases as chain length is increased, while the intermediate length peptide A12 has the highest β-sheet growth rate in the second stage. β-sheet growth behavior of A24 on the surface still fits negative exponential model. Overall, the hydrophobic surface accelerates β-sheet growth by enhancing local concentration and reducing conformational entropy of poly(A) peptide, and the β-sheet growth of the intermediate length peptide A12 is the fastest on the surface. Our simulation results shed light on understanding the accelerated peptide fibrillization on the hydrophobic surface.