Infrared Laser-Induced Amyloid Fibril Dissociation: A Joint Experimental/Theoretical Study on the GNNQQNY Peptide

Takayasu Kawasaki, Viet Hoang Man, Yasunobu Sugimoto, Nobuyuki Sugiyama, Hiroko Yamamoto, Koichi Tsukiyama, Junmei Wang, Philippe Derreumaux, Phuong H. Nguyen

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Neurodegenerative diseases are usually characterized by plaques made of well-ordered aggregates of distinct amyloid proteins. Dissociating these very stable amyloid plaques is a critical clinical issue. In this study, we present a joint mid-infrared free electron laser experiment/nonequilibrium molecular dynamics simulation to understand the dissociation process of a representative example GNNQQNY fibril. By tuning the laser frequency to the amide I band of the fibril, the resonance takes place and dissociation is occurred. With the calculated and observed wide-angle X-ray scattering profiles and secondary structures before and after laser irradiation being identical, we can propose a dissociation mechanism with high confidence from our simulations. We find that dissociation starts in the core of the fibrils by fragmenting the intermolecular hydrogen bonds and separating the peptides and then propagates to the fibril extremities leading to the formation of unstructured expanded oligomers. We suggest that this should be a generic mechanism of the laser-induced dissociation of amyloid fibrils.

Original languageEnglish (US)
Pages (from-to)6266-6277
Number of pages12
JournalJournal of Physical Chemistry B
Volume124
Issue number29
DOIs
StatePublished - Jul 23 2020
Externally publishedYes

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

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