Drastic acceleration of fibrillation of insulin by transient cavitation bubble |
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| Affiliation: | 1. Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531, Japan;2. Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan;1. Vassar College, 124 Raymond Ave, Poughkeepsie, NY 12604, USA;2. SUNY Maritime College, Throggs Neck, NY 10465, USA;3. Antonelli Research and Technology, 3227 SE Lambert St, Portland, OR 97202, USA;1. Department of Chemistry, Technical University of Denmark, Kgs. Lyngby, Denmark;2. Center for Electron Nanoscopy, Technical University of Denmark, Kgs. Lyngby, Denmark;3. Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark;4. CMC assist ApS, Copenhagen, Denmark;1. School of Mechanical Engineering, Tianjin University, 300350 Tianjin, China;2. Institute of Engineering Mechanics, Beijing Jiaotong University, 100044 Beijing, China;3. Institut FEMTO-ST, Université Bourgogne Franche-Comté, CNRS, F-25030 Besançon Cedex, France |
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| Abstract: | Amyloid-fibril formation of proteins can be accelerated by ultrasonic irradiation to the peptide solutions. Although this phenomenon contributes to understanding pathogenic behavior of amyloidosis, its physical mechanism has not been clarified, because several factors (cavitation, temperature increase, stirring effect, and so on) related to ultrasonic irradiation can participate in the fibrillation reaction. Here, we independently study contributions of the possible factors, using insulin, which is extremely stable and then suitable for the mechanism clarification. We find that the optimized ultrasonic irradiation can drastically accelerate the fibrillation reaction; the time for completing the reaction is shortened compared with the high-speed (1200 rpm) stirring agitation by a factor of 430. The fibrillation reaction proceeds only when the subharmonic-mode intensity exceeds a threshold, indicating generation of the transient cavitation bubbles. Our results reveal that not the temperature increase but the transient cavitation bubbles work as the dominant accelerator of the fibrillation reaction. |
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| Keywords: | Aggregation acceleration Transient bubbles Subharmonic wave Amyloid fibril Acoustic field analysis |
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