Pathological Folding of α-Synuclein on Polystyrene Nanoplastic Revealed by Sum Frequency Scattering and 2D Infrared Spectroscopy.

The impact of micro- and nanoplastics (MNPs) on human health is a growing field of research. Reports that MNPs can breach the blood-brain barrier and accumulate inside the brain have raised concerns over their possible involvement in the development of neurogenerative diseases. The aggregation of the abundant neuronal protein α-synuclein (α-syn) is pertinent to almost 50 neurological diseases including Parkinson's disease (PD). The role of nanoplastics in the formation of toxic aggregates is unclear and has been shown to depend strongly on the type of plastics. Here we report the molecular structure and orientation of human α-syn adsorbed on polystyrene NPs using interface-specific sum frequency scattering (SFS) and structure-sensitive two-dimensional infrared (2D IR) spectroscopy. The SFS experimental data were compared with the calculated spectra of several thousands of α-syn conformations generated from molecular dynamics simulations. The SFS results reveal that α-syn folds on polystyrene nanoplastics, adopting a partly helical structure with the N-terminus and nonamyloid component regions directly bound on the polystyrene nanosurface, while the C terminus protrudes away from the polystyrene interface. 2D IR results suggest that the entire α-syn corona comprises of partly aggregated α-syn structures, built of an ordered core enclosed with flexible dynamic regions. The data shed light on the mechanism by which α-syn folds and forms aggregates at the plastic particle surfaces, a link that has been missing in understanding the role of nanoplastic in the pathogenesis of PD and related neurodegenerative diseases.