Curved Nanointerface Controls the Chiral Effect on Peptide Fibrillation

Area of Science:

• Biomaterials Science
• Nanotechnology
• Neuroscience

Background:

• Amyloid-β (Aβ) peptide fibrillation is central to Alzheimer's disease pathogenesis.
• Nanostructures are explored to inhibit Aβ fibrillation, but the role of chirality at curved interfaces remains unclear.

Purpose of the Study:

• To investigate the curvature-modulated chiral effect of gold nanoparticles on Aβ1-42 fibrillation.
• To explore the potential of chiral nanoparticles as inhibitors for anti-amyloidosis therapies.

Main Methods:

• Synthesis and characterization of chiral l/d-penicillamine-gold nanoparticles (l/d-PGNPs) with varying curvatures.
• Microscopic and spectroscopic analyses to study Aβ1-42 fibrillation.
• Assessment of Aβ1-42 peptide cytotoxicity after inhibition.

Main Results:

• Highly curved d-PGNPs (0.2 nm⁻¹) demonstrated effective suppression of Aβ1-42 fibrillation with chiral selectivity.
• Inhibition occurred at a low inhibitor/peptide molar ratio (1:100).
• Reduced cytotoxicity of Aβ1-42 peptides was observed post-inhibition.

Conclusions:

• Curvature and chirality of nanointerfaces significantly modulate Aβ1-42 fibrillation.
• The curved d-nanointerface enhances inhibition by controlling spatial arrangement and interactions with Aβ1-42.
• Findings provide insights for developing novel anti-amyloidosis inhibitors based on chiral nano-bio interactions.