Curved Nanointerface Controls the Chiral Effect on Peptide Fibrillation

Nanostructures with varying functionalities have been engineered to modulate the fibrillation of amyloid-β (Aβ) peptides. Nevertheless, the chirality effect at the curved nanointerfaces is seldom dissected. In this study, we systematically explored the curvature-modulated chiral effect on the regulation of Aβ1–42 fibrillation by using l/d-penicillamine-gold nanoparticles (l/d-PGNPs). According to the microscopic and spectroscopic analyses, Aβ1–42 fibrillation can be effectively suppressed by more curved (0.2 nm–1, 1/r) d-nanointerface (d-PGNPs5) with notable chiral selectivity, even at a low inhibitor/peptide (I/P) molar ratio (1:100). A greatly alleviated cytotoxic effect of Aβ1–42 peptides after the inhibition process is also revealed. The highly curved nanointerface drives the formation of multiple hydrogen bonds and promotes electrostatic interactions with Aβ1–42. Importantly, the curved d-nanointerface controls well the spatial arrangement of Pen motifs, making it incompatible with the fibrillation direction of Aβ1–42 and thus gaining enhanced efficiency on amyloid fibrillar modulation. This study provides valuable insights into the interactions between chirality and peptide-nanointerface effects, which are crucial for the development of inhibitors in anti-β-amyloidosis.