Fibrillation of Human Serum Albumin Differentially Affected by Asp-, Arg-, and Tyr-Capped Gold Nanoparticles.

Abstract

Fibrillation of proteins is associated with a number of debilitating diseases, including various neurodegenerative disorders. Prevention of the protein fibrillation process is therefore of immense importance. We investigated the effect of amino acid-capped AuNPs on the prevention of the fibrillation process of human serum albumin (HSA), a model protein. Amino acid-capped AuNPs of varying sizes and agglomeration extents were synthesized under physiological conditions. The AuNPs were characterized by their characteristic surface plasmon resonance (SPR), and their interactions with HSA were investigated through emission spectroscopy in addition to circular dichroism (CD) spectral analyses. Fluorescence lifetime imaging (FLIM) as well as transmission electron microscopy (TEM) were used to observe the fibrillar network. Thermodynamic and kinetic analyses from CD and fluorescence emission spectra provided insights into the fibrillation pathway adopted by HSA in the presence of capped AuNPs. Kinetics of the fibrillation pathway followed by ThT fluorescence emission confirmed the sigmoidal nature of the process. The highest cooperativity was observed in the case of Asp-AuNPs with HSA. This was in accordance with the ΔG value obtained from the CD spectral analyses, where Arg-AuNPs with HSA showed the highest positive ΔG value and Asp-AuNPs with HSA showed the most negative ΔG value. The study provides information about the potential use of conjugate AuNPs to monitor the fibrillation process in proteins.