Effects of amino acid-functionalized silver nanoparticles on lysozyme amyloid fibrillogenesis

Amyloid fibrillogenesis of proteins have been considered as the major cause behind several degenerative diseases. Nanoparticles have been found to have great potential as a substrate for designing amyloid fibril inhibitors and/or modulators. This is mainly due to its ideal characteristics, such as small size, high surface area-to volume ratio, and modifiable surface. This study is aimed at examining the influence of amino acid-modified silver nanoparticles on amyloid fibril formation. We first synthesized and characterized the proline- and cysteine-functionalized silver nanoparticles (Pro-AgNP and Cys-AgNP). Next, the effects of functionalized silver nanoparticles on amyloid fibrillogenesis and structural changes of hen lysozyme were examined using various spectroscopic and biophysical tools. Our results showed that Pro-AgNP/Cys-AgNP dose-dependently suppressed lysozyme amyloid fibrillogenesis, whereas negligible fibril-inhibiting effect was observed in the bare AgNP or proline/cysteine. Moreover, reduced solvent exposure and α-to-β transition were detected in lysozyme upon the addition of Pro-AgNP/Cys-AgNP. Finally, the nature of interactions between lysozyme and Pro-AgNP/Cys-AgNP was further examined using fluorescence quenching and molecular docking. By altering the properties of nanoparticles to design suitable nanoprobes, we have shown that amyloid fibrillogenesis can be controlled.