title: Drastic acceleration of fibrillation of insulin by transient cavitation bubble.
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 (1200rpm) 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.
authors.affiliation: Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531, Japan.
authors.forename: Kichitaro
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nishioka
authors.affiliation: Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hirao
authors.affiliation: Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Masatomo
authors.initials: M
authors.lastname: So
authors.affiliation: Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Goto
authors.affiliation: Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Ogi
mesh_terms: D007328:Insulin / Q000737:chemistry*; D007700:Kinetics; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D000069453:Ultrasonic Waves
chemical_list: D007328:Insulin
keywords: Acoustic field analysis; Aggregation acceleration; Amyloid fibril; Subharmonic wave; Transient bubbles