Effect of carbonaceous ultrafine particles on the structure and oligomerization of Aβ₄₂ peptide

The impact of pervasive air pollutants on human health is a growing concern in scientific communities. Among different air pollutants, ultrafine particles (UFPs; with aerodynamic diameter <100 nm) might pass through biological barriers and have a severe impact on human health, including early progression of neurodegenerative diseases such as Alzheimer's disease (AD). A significant fraction of UFPs consists of carbonaceous compounds, composed of elemental and organic carbon (EC and OC). While in-vivo experimental studies showed the neurotoxicity of typical OC and polycyclic aromatic hydrocarbons (PAHs), the molecular interactions involved in the progression of AD remain unclear. In this study, molecular dynamics simulations were performed to investigate the impact of carbonaceous UFPs on the structure of the Aβ₄₂ monomer and the oligomerization of four Aβ₄₂ peptides, associated with the development of AD. For the simulations, a fullerene (C₆₀) was used for the modeling of EC, while benzo [a]pyrene (B[a]P) was used for the modeling of OC. The results revealed that the presence of C₆₀ accelerated the tetramerization of Aβ₄₂ peptides by 2.5 times, while C₆₀/B[a]P promoted the unfolding of the peptide monomer showing the strongest interactions with the Aβ₄₂ monomer. Similarly, C₆₀/4B[a]P decreased the number of helices in the secondary structure of the peptide monomer by 60%. The simplified UFP models in this study, promoted the early aggregation of peptides to dimers, suggesting the progression of AD.