A Condensation-Ordering Mechanism in Nanoparticle-Catalyzed Peptide Aggregation

TL;DR

This study uses molecular dynamics simulations to elucidate how nanoparticles catalyze peptide aggregation, revealing a two-phase process involving initial oligomer assembly followed by beta-sheet formation.

Contribution

It provides a detailed molecular mechanism of nanoparticle-induced peptide aggregation, highlighting the sequential formation of disordered oligomers and ordered beta-sheets.

Findings

Nanoparticles promote peptide aggregation via a two-phase process.

Disordered oligomers assemble onto nanoparticles before forming beta-sheets.

Simulation timescale captures millisecond-scale aggregation dynamics.

Abstract

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 beta-sheets as their size increases.