Unveiling the interaction of protein fibrils with gold nanoparticles by plasmon enhanced nano-spectroscopy.

The development of various degenerative diseases is suggested to be triggered by the uncontrolled organisation and aggregation of proteins into amyloid fibrils. For this reason, there are ongoing efforts to develop novel agents and approaches, including metal nanoparticle-based colloids, that dissolve amyloid structures and prevent pathogenic protein aggregation. In this contribution, the role of gold nanoparticles (AuNPs) in degrading amyloid fibrils of the model protein lysozyme is investigated. The amino acid composition of fibril surfaces before and after the incubation with AuNPs is determined at the single fibril level by exploiting the high spatial resolution and sensitivity provided by tip-enhanced and surface-enhanced Raman spectroscopies. This combined spectroscopic approach allows to reveal the molecular mechanisms driving the interaction between fibrils and AuNPs. Our results provide an important input for the understanding of amyloid fibrils and could have a potential translational impact on the development of strategies for the prevention and treatment of amyloid-related diseases.