Kinetic pathways to peptide aggregation on surfaces: the effects of β-sheet propensity and surface attraction

Mechanisms of peptide aggregation on hydrophobic surfaces are explored using molecular dynamics simulations with a coarse-grained peptide representation. Systems of peptides are studied with varying degrees of backbone rigidity (a measure of β-sheet propensity) and degrees of attraction between their hydrophobic residues and the surface. Multiple pathways for aggregation are observed, depending on the surface attraction and peptide β-sheet propensity. For the case of a single-layered β-sheet fibril forming on the surface (a dominant structure seen in all simulations), three mechanisms are observed: (a) a condensation-ordering transition where a bulk-formed amorphous aggregate binds to the surface and subsequently rearranges to form a fibril; (b) the initial formation of a single-layered fibril in the bulk depositing flat on the surface; and (c) peptides binding individually to the surface and nucleating fibril formation by individual peptide deposition. Peptides with a stiffer chiral backbone prefer mechanism (b) over (a), and stronger surface attractions prefer mechanism (c) over (a) and (b). Our model is compared to various similar experimental systems, and an agreement was found in terms of the surface increasing the degree of fibrillar aggregation, with the directions of fibrillar growth matching the crystallographic symmetry of the surface. Our simulations provide details of aggregate growth mechanisms on scales inaccessible to either experiment or atomistic simulations.