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.

Time-Resolved Observation of Evolution of Amyloid-β Oligomer with Temporary Salt Crystals

“…Previous studies 51,52 demonstrated the importance of the liquid-solid interface or the gas-liquid interface as the monomer adsorber; the interfaces dramatically accelerate the aggregation process of amyloidogenic proteins. Furthermore, we previously showed that the shrinking interface highly promotes the nucleation reaction of protein aggregates through the local condensation of the attached proteins, [53][54][55] as illustrated in Fig. S7: Ultrasonic cavitation, i.e.…”

Formation and properties of amyloid fibrils of prion protein

“…Although the effects of agitation may be similar to those of ultrasonication, the cavitation bubbles which lead to the breakdown of supersaturation and ultimately to fibrillation are only generated under ultrasonication. In their comparison of high-speed stirring agitation at 1200 rpm and ultrasonication, Nakajima et al (2017) observed that ultrasonication significantly accelerated the fibrillation reaction.…”

Effect mechanism of ultrasound pretreatment on fibrillation Kinetics, physicochemical properties and structure characteristics of soy protein isolate nanofibrils

“…So et al [28] proposed that fibril formation was mostly limited by the high free-energy barrier, and ultrasound could reduce the high free-energy barrier effectively. Nakajima et al [29] found the transient cavitation bubbles produced by ultrasound accelerated the fibrillation reaction. In summary, it can be referred that ultrasound could regulate protein fibrillation through some specific approaches.…”