Probing the Protein Folding Energy Landscape: Dissociation of Amyloid-β Fibrils by Laser-Induced Plasmonic Heating

Insoluble amyloid fibrils made from proteins and peptides are difficult to be degraded in both living and artificial systems. The importance of studying their physical stability lies primarily with their association with human neurodegenerative diseases, but also owing to their potential role in multiple bio-nanomaterial applications. Here, gold nanorods (AuNRs) were utilized to investigate the plasmonic heating properties and dissociation of amyloid-β fibrils formed by different peptide fragments (Aβ16–22/Aβ25–35/Aβ1–42) related to the Alzheimer's disease. It is demonstrated that AuNRs were able to break mature amyloid-β fibrils from both the full length (Aβ1–42) and peptide fragments (Aβ16–22/Aβ25–35) within minutes by triggering ultrahigh localized surface plasmon resonance (LSPR) heating. The LSPR energy absorbed by the amyloids to unfold and move to higher levels in the protein folding energy landscape can be measured directly and in situ by luminescence thermometry using lanthanide-based upconverting nanoparticles. We also show that Aβ16–22 fibrils, with the largest persistence length, displayed the highest resistance to breakage, resulting in a transition from rigid fibrils to short flexible fibrils. These findings are consistent with molecular dynamics simulations indicating that Aβ16–22 fibrils possess the highest thermostability due to their highly ordered hydrogen bond networks and antiparallel β-sheet orientation, hence affected by an LSPR-induced remodeling rather than melting. The present results introduce original strategies for disassembling amyloid fibrils noninvasively in liquid environment; they also introduce a methodology to probe the positioning of amyloids on the protein folding and aggregation energy landscape via nanoparticle-enabled plasmonic and upconversion nanothermometry.