Multiscale Aggregation of the Amyloid Aβ16-22 Peptide: From Disordered Coagulation and Lateral Branching to Amorphous Prefibrils.

In this work we investigate the multiscale dynamics of the aggregation process of an amyloid peptide, Aβ16-22. By performing massive coarse-grained simulations at the quasi-atomistic resolution and including hydrodynamic effects, we followed the formation and growth of a large elongated aggregate and its slow structuring. The elongation proceeds via a two-step nucleation mechanism with disordered aggregates formed initially and subsequently fusing to elongate the amorphous prefibril. A variety of coagulation events coexist, including lateral growth. The latter mechanism, sustained by long-range hydrodynamics correlations, actually can create a large branched structure spanning a few tens of nanometers. Our findings confirm the experimental hypothesis of a critical contribution of lateral growth to the amyloid aggregation kinetics and the capability of our model to sample critical structures like prefibril hosting annular pores.