Inhibition of amyloid fibrillation of human γD-crystallin by gold nanoparticles: Studies at molecular level

Abstract The capability of citrate-stabilized gold nanoparticles (AuNps) has been explored for the inhibition of amyloid fibrillation of human γD-crystallin (HGD), a major protein of eye lens. Citrate-capped AuNps were synthesized, characterized and used further for amyloid inhibition. The results from intrinsic and extrinsic (in the presence of Thioflavin T and ANS) fluorescence based assays and CD spectroscopy clearly suggest that AuNps at nanomolar concentrations can act as an effective inhibitor against fibrillation of HGD. Fluorescence microscopic and transmission electron microscopic images also supported this observation. Considering the inhibitory role of AuNps against HGD fibrillation, interactions between HGD and AuNps were studied to decipher the mechanism of amyloid inhibition. The binding and quenching constants were calculated as ~109 M−1 using the data of tryptophan fluorescence quenching of HGD by AuNps. Ground state complexation between the protein and nanoparticles was predicted. AuNps were not found to cause any major conformational changes in the native protein. Entropy-driven complexation process between the protein and nanoparticles indicates the interactions of AuNps with hydrophobic residues of HGD. Therefore, in the presence of AuNps, the exposure of the hydrophobic patches of HGD during its partial unfolding became restricted, which results inhibition in HGD fibrillation.