Probing the effect of the molecular interface of gold nanoparticles on the disassembly of insulin amyloid fibrils

Aberrant protein aggregation into amyloid fibrils underlies the onset of several degenerative pathologies, requiring increasing efforts to identify ever newer approaches to prevent their formation and to disassemble toxic amyloid structures. In this context, gold nanoparticles (AuNPs) show great promise, thanks to their ability to chemically interact with proteins while simultaneously serving as local spectroscopic probes due to their peculiar optical properties. Here, we investigate the role of the surface chemistry of AuNPs in the disassembly of insulin amyloid fibrils. By taking advantage of the remarkable sensitivity and spatial resolution of surface enhanced Raman spectroscopy, we elucidate the molecular mechanisms driving fibril-AuNP interaction at the nanoscale, identifying the amino acids directly involved. The obtained results will serve as a benchmark for developing novel diagnostic and therapeutic strategies employing AuNPs for the treatment of amyloid-related diseases.