Nucleus factory on cavitation bubble for amyloid β fibril

Abstract

Structural evolution from monomer to fibril of amyloid β peptide is related to pathogenic mechanism of Alzheimer disease, and its acceleration is a long-running problem in drug development. This study reveals that ultrasonic cavitation bubbles behave as catalysts for nucleation of the peptide: The nucleation reaction is highly dependent on frequency and pressure of acoustic wave, and we discover an optimum acoustical condition, at which the reaction-rate constant for nucleation is increased by three-orders-of magnitudes. A theoretical model is proposed for explaining highly frequency and pressure dependent nucleation reaction, where monomers are captured on the bubble surface during its growth and highly condensed by subsequent bubble collapse, so that they are transiently exposed to high temperatures. Thus, the dual effects of local condensation and local heating contribute to dramatically enhance the nucleation reaction. Our model consistently reproduces the frequency and pressure dependences, supporting its essential applicability.

Heparin‐induced amyloid fibrillation of β2‐microglobulin explained by solubility and a supersaturation‐dependent conformational phase diagram

“…Although we used ultrasonication to accelerate fibrillation in the present study, the basic mechanism underlying heparin‐dependent acceleration will be independent of the methodology of acceleration. The generation of an air‐liquid interface by various agitations including stirring or ultrasonication induces high local concentrations of target proteins at the surface of the interface and is considered to be responsible for the acceleration of fibrillation . Our approach of ultrasonication is highly effective for generating air‐liquid interactions by cavitation, which appears and disappears periodically, further increasing protein concentrations with elevations in temperature .…”

“…The generation of an air‐liquid interface by various agitations including stirring or ultrasonication induces high local concentrations of target proteins at the surface of the interface and is considered to be responsible for the acceleration of fibrillation . Our approach of ultrasonication is highly effective for generating air‐liquid interactions by cavitation, which appears and disappears periodically, further increasing protein concentrations with elevations in temperature . Lipid membranes including vesicles and lipid bilayers bind to various amyloidogenic proteins or peptides and accelerate fibrillation both in vivo and in vitro .…”

“…50,51 Our approach of ultrasonication is highly effective for generating air-liquid interactions by cavitation, which appears and disappears periodically, further increasing protein concentrations with elevations in temperature. 51 Lipid membranes including vesicles and lipid bilayers bind to various amyloidogenic proteins or peptides and accelerate fibrillation both in vivo and in vitro. 19,[52][53][54][55][56] Irrespective of the methodologies and experimental conditions employed, acceleration based on the anion effects of heparin are likely to occur, in which the positively charged regions of proteins are targets of interactions even when the protein's net charge is not positive.…”

Evidence for a central role of PrP helix 2 in the nucleation of amyloid fibrils

“…This FW model has been widely used to analyze the aggregation kinetics of various proteins, including PrP (57-59), amyloid b (58), t (59), b 2 -microglobulin (45,60), and other types of amyloidogenic proteins (26,57,61). The conventional TS theory was subsequently used to connect k nuc to the free-energy barrier of nucleation (ΔG ‡ ) (Eq.…”

Proteome analysis of tissues by mass spectrometry

“…(a) Ultrasonication. Reproduced with permission from Nakajima et al () copyright year 2016 (Nature publishing group) (b) Pressure based systems. Reproduced with permission from Shao, Guo, & Aebersold () copyright year 2015 (Elsevier).…”