β-sheet propensity controls the kinetic pathways and morphologies of seeded peptide aggregation

The effect of seeds in templating the morphology of peptide aggregates is examined using molecular dynamics simulations and a coarse-grained peptide representation. Varying the nature of the aggregate seed between β-sheet, amorphous, and β-barrel seeds leads to different aggregation pathways and to morphologically different aggregates. Similar effects are seen by varying the β-sheet propensity of the free peptides. For a fibrillar seed and free peptides of high β-sheet propensity, fibrillar growth occurred by means of direct attachment (without structural rearrangement) of free individual peptides and small ordered oligomers onto the seed. For a fibrillar seed and free peptides of low β-sheet propensity, fibrillar growth occurred through a dock-lock mechanism, in which the free peptides first docked onto the seed, and then locked on, extending and aligning to join the fibril. Amorphous seeds absorbed free peptides into themselves indiscriminately, with any fibrillar rearrangement subsequent to this absorp...