title: Picosecond pulsed infrared laser tuned to amide I band dissociates polyglutamine fibrils in cells.
abstract: Amyloid fibrils are causal substances for serious neurodegenerative disorders and amyloidosis. Among them, polyglutamine fibrils seen in multiple polyglutamine diseases are toxic to neurons. Although much efforts have been made to explore the treatments of polyglutamine diseases, there are no effective drugs to block progression of the diseases. We recently found that a free electron laser (FEL), which has an oscillation wavelength at the amide I band (C = O stretch vibration mode) and picosecond pulse width, was effective for conversion of the fibril forms of insulin, lysozyme, and calcitonin peptide into their monomer forms. However, it is not known if that is also the case in polyglutamine fibrils in cells. We found in this study that the fibril-specific β-sheet conformation of polyglutamine peptide was converted into nonfibril form, as evidenced by the infrared microscopy and scanning-electron microscopy after the irradiation tuned to 6.08 μm. Furthermore, irradiation at this wavelength also changed polyglutamine fibrils to their nonfibril state in cultured cells, as shown by infrared mapping image of protein secondary structure. Notably, infrared thermography analysis showed that temperature increase of the cells during the irradiation was within 1 K, excluding thermal damage of cells. These results indicate that the picosecond pulsed infrared laser can safely reduce amyloid fibril structure to the nonfibril form even in cells.
authors.affiliation: IR Free Electron Laser Research Center, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Takayasu
authors.initials: T
authors.lastname: Kawasaki
authors.affiliation: IR Free Electron Laser Research Center, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Gaku
authors.initials: G
authors.lastname: Ohori
authors.affiliation: IR Free Electron Laser Research Center, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Chiba
authors.affiliation: IR Free Electron Laser Research Center, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsukiyama
authors.affiliation: Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, 3-39-22, showa-machi, Maebashi, Gunma, 371-8511, Japan. knakamur@gunma-u.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakamura
mesh_terms: D000577:Amides / Q000737:chemistry*; D000682:Amyloid / Q000528:radiation effects*; D004583:Electrons; D057809:HEK293 Cells; D006801:Humans; D007259:Infrared Rays; D007834:Lasers; D008855:Microscopy, Electron, Scanning; D010455:Peptides / Q000528:radiation effects*; D013817:Thermography; D013997:Time Factors
chemical_list: D000577:Amides; D000682:Amyloid; D010455:Peptides; C097188:polyglutamine
keywords: Amide I band; Amyloid fibrils; Free electron laser; Infrared microscopy; Polyglutamine disease; β-Sheet