Author(s)

Takayasu Kawasaki, Toyonari Yaji, Takayuki Imai, Toshiaki Ohta, Koichi Tsukiyama

IR Free Electron Laser Research Center, Research Institute for Science and Technology (RIST), Tokyo University of Science, Noda, Japan.
SR Center, Research Organization of Science and Engineering, Ritsumeikan University, Kusatsu, Japan.

Amyloid fibrils are widely recognized as a cause of serious amyloidosis such as Alzheimer’s disease. Although dissociation of amyloid fibril aggregates is expected to lead to a decrease in the toxicity of the fibrils in cells, the fibril structure is robust under physiological conditions. We have irradiated amyloid fibrils with a free-electron laser (FEL) tuned to mid-infrared frequencies to induce dissociation of the aggregates into monomer forms. We have previously succeeded in dissociating fibril structures of a short peptide of the thyroid hormone by tuning the oscillation frequency to the amide I band, but the detailed structural changes of the peptide have not yet been determined at a high spatial resolution. Synchrotron-radiation infrared microscopy (SR-IRM) is a powerful tool for in situ analysis of minute structural changes of various materials, and in this study, the feasibility of SR-IRM for analyzing the microscopic conformational changes of amyloid fibrils after FEL irradiation was investigated. Reflection spectra of the amyloid fibril surface showed that the amide I peaks shifted to higher wave numbers after the FEL irradiation, indicating that the initial β-sheet-rich structure transformed into a mixture of non-ordered and turn-like peptide conformations. This result demonstrates that conformational changes of the fibril structure after the FEL irradiation can be observed at a high spatial resolution using SR-IRM analysis and the FEL irradiation system can be useful for dissociation of amyloid aggregates.

Amyloid Fibrils, Free-Electron Laser, Infrared Microscopy, Synchrotron Radiation

Kawasaki, T. , Yaji, T. , Imai, T. , Ohta, T. and Tsukiyama, K. (2014) Synchrotron-Infrared Microscopy Analysis of Amyloid Fibrils Irradiated by Mid-Infrared Free-Electron Laser. American Journal of Analytical Chemistry, 5, 384-394. doi: 10.4236/ajac.2014.56047.