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

resumo

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-beta fibrils formed by different peptide fragments (A beta 16-22/A beta 25-35/A beta 1-42) related to the Alzheimer's disease. It is demonstrated that AuNRs were able to break mature amyloid-beta fibrils from both the full length (A beta 1-42) and peptide fragments (A beta 16-22/A beta 25-35) 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 A beta 16-22 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 A beta 16-22 fibrils possess the highest thermostability due to their highly ordered hydrogen bond networks and antiparallel beta-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.

palavras-chave

GOLD NANOPARTICLES; CORONA COMPOSITION; AGGREGATION; PEPTIDE; NANOCRYSTALS; RECOGNITION; DISSOLUTION; NANORODS

categoria

Chemistry; Science & Technology - Other Topics; Materials Science

autores

Lin, DD; Qian, ZY; Bagnani, M; Hernández-Rodríguez, MA; Corredoira-Vázquez, J; Wei, GH; Carlos, LD; Mezzenga, R

Grupos

G2 - Materiais Fotónicos, Eletrónicos e Magnéticos

Projectos

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)

The shape of water: Nanothermometry as a tool to unveil the structure of liquid water and water-based nanofluids (THE SHAPE OF WATER )

agradecimentos

This work was supported by Qian Xuesen Collaborative Research Center of Astrochemistry and Space Life Sciences Fund and K. C. Wong Magna Fund in Ningbo University. This work was also developed within the scope of the projects CICECO-Aveiro Institute of Materials (UIDB/50011/2020, UIDP/50011/2020, and LA/P/0006/2020) and The Shape of Water (PTDC/NAN-PRO/3881/2020) financed by Portu-guese funds through the FCT/MEC (PIDDAC) . Simulations were performed at the High-Performance Computing Server of Ningbo University and Computing Biomechanics Center of Shanghai University of Sport. The authors thank Prof. X. Liu, who kindly provided the UCNPs, Prof. W. Wan, who gave help with the tracking algorithm, Prof. M. Ji, who provided the fs-laser system, Dr. Wei Long Soon, who gave useful suggestions, and Prof. Carlos Brites for fruitful discussions concerning the temperature transient curves. J.C.V. also thanks Xunta de Galicia for his postdoctoral fellowship.