Effect of Zinc Oxide Nanoparticles Size/Surface Curvature on α-synuclein Amyloidogenesis

Abstract

The work focuses on investigating the effect of ZnONP and its varying size (30, 60 and 120 nm) on α-synuclein fibrillation process at physiological conditions. α-Synuclein adsorbs strongly onto the surface of ZnONP, observed using different biophysical techniques like UVvisible spectroscopy, Zeta sizer etc. The ThT assay shows inhibition of α-synuclein fibrillation in presence of different curvature ZnONPs with increased lag time and decreased growth rate. Native α-synuclein has shown to form long unbranched fibrils rich in β-sheet structure, whereas ZnONP interface with larger curvature (120 nm) take the protein off-pathway aggregates faster than any other studied curvature/sizes. Though the secondary and tertiary structure analysis by CD and fluorescence spectroscopy showed that the protein in α-synuclein-ZnONPs aggregate retained the native structure and showed insignificant toxicity towards human neuroblastoma cells (IMR-32). These findings suggest that the inhibitory effect of ZnONP on αsynuclein fibrillation is determined by its surface physicochemical properties, including the size/curvature of nanoparticles. The study offers new insight on the therapeutic potential of ZnONP in combating pathologies related to αsynuclein-mediated amyloidogenesis.