Abstract
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.
Highlights
Amyloidosis is caused by the deposition of amyloid fibrils in various organs of a mammalian body [1]-[3]
Synchrotron radiation IR microscopy (SR-IRM) has recently been used for monitoring the protein secondary structures of silk and investigating protein phosphorylation in living cells [25] [26]. Encouraged by these studies, we investigated the use of synchrotron radiation (SR)-IRM for detecting the minute structural changes of amyloid fibrils formed by a short peptide after irradiation with an free-electron laser (FEL) tuned to the amide I band
After the FEL irradiation tuned to 6.08 μm, we confirmed the effect of FEL on the disaggregation of the peptide fibrils by using SEM
Summary
Amyloidosis is caused by the deposition of amyloid fibrils in various organs of a mammalian body [1]-[3]. We have recently found that a free-electron laser (FEL) tuned to the amide I band (1600 - 1700 cm−1) is able to dissociate the amyloid fibrils of lysozyme and of a five-residue peptide (DFNKF) of the thyroid hormone [8] [9]. Synchrotron radiation IR microscopy (SR-IRM) has recently been used for monitoring the protein secondary structures of silk and investigating protein phosphorylation in living cells [25] [26] Encouraged by these studies, we investigated the use of SR-IRM for detecting the minute (conformational) structural changes of amyloid fibrils formed by a short peptide after irradiation with an FEL tuned to the amide I band
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