A Condensation-Ordering Mechanism in Nanoparticle-Catalyzed Peptide Aggregation

Nanoparticles introduced in living cells are capable of strongly promoting the aggregation of peptides and proteins. We use here molecular dynamics simulations to characterise in detail the process by which nanoparticle surfaces catalyse the self-assembly of peptides into fibrillar structures. The simulation of a system of hundreds of peptides over the millisecond timescale enables us to show that the mechanism of aggregation involves a first phase in which small structurally disordered oligomers assemble onto the nanoparticle and a second phase in which they evolve into highly ordered as their size increases.Author Summary: Protein misfolding and aggregation are associated with a wide variety of human disorders, which include Alzheimer's and Parkinson's diseases and late onset diabetes. It has been recently realised that the process of aggregation may be triggered by the presence of nanoparticles. We use here molecular dynamics simulations to characterise the molecular mechanism by which such nanoparticles are capable of enhancing the rate of formation of peptide aggregates. Our findings indicate that nanoparticle surfaces act as a catalyst that increases the local concentration of peptides, thus facilitating their subsequent assembly into stable fibrillar structures. The approach that we present, in addition to providing a description of the process of aggregation of peptides in the presence of nanoparticles, will enable the study of the mechanism of action of a variety of other potential aggregation-promoting agents present in living organisms, including lipid membranes and other cellular components.