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Nucleus factory on cavitation bubble for amyloid ? fibril.

ABSTRACT: Structural evolution from monomer to fibril of amyloid ? 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.

SUBMITTER: Nakajima K

PROVIDER: S-EPMC4766559 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Nucleus factory on cavitation bubble for amyloid β fibril.

Nakajima Kichitaro K Ogi Hirotsugu H Adachi Kanta K Noi Kentaro K Hirao Masahiko M Yagi Hisashi H Goto Yuji Y

Scientific reports 20160225

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 t ...[more]

PMID: 26912021

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Project description:Sonoporation is the membrane disruption generated by ultrasound and has been exploited as a non-viral strategy for drug and gene delivery. Acoustic cavitation of microbubbles has been recognized to play an important role in sonoporation. However, due to the lack of adequate techniques for precise control of cavitation activities and real-time assessment of the resulting sub-micron process of sonoporation, limited knowledge has been available regarding the detail processes and correlation of cavitation with membrane disruption at the single cell level. In the current study, we developed a combined approach including optical, acoustical, and electrophysiological techniques to enable synchronized manipulation, imaging, and measurement of cavitation of single bubbles and the resulting cell membrane disruption in real-time. Using a self-focused femtosecond laser and high frequency ultrasound (7.44MHz) pulses, a single microbubble was generated and positioned at a desired distance from the membrane of a Xenopus oocyte. Cavitation of the bubble was achieved by applying a low frequency (1.5MHz) ultrasound pulse (duration 13.3 or 40?s) to induce bubble collapse. Disruption of the cell membrane was assessed by the increase in the transmembrane current (TMC) of the cell under voltage clamp. Simultaneous high-speed bright field imaging of cavitation and measurements of the TMC were obtained to correlate the ultrasound-generated bubble activities with the cell membrane poration. The change in membrane permeability was directly associated with the formation of a sub-micrometer pore from a local membrane rupture generated by bubble collapse or bubble compression depending on ultrasound amplitude and duration. The impact of the bubble collapse on membrane permeation decreased rapidly with increasing distance (D) between the bubble (diameter d) and the cell membrane. The effective range of cavitation impact on membrane poration was determined to be D/d=0.75. The maximum mean radius of the pores was estimated from the measured TMC to be 0.106±0.032?m (n=70) for acoustic pressure of 1.5MPa (duration 13.3?s), and increased to 0.171±0.030?m (n=125) for acoustic pressure of 1.7MPa and to 0.182±0.052?m (n=112) for a pulse duration of 40?s (1.5MPa). These results from controlled cell membrane permeation by cavitation of single bubbles revealed insights and key factors affecting sonoporation at the single cell level.

Project description:Precise and high-speed sorting of individual target cells from heterogeneous populations plays an imperative role in cell research. Although the conventional fluorescence-activated cell sorter (FACS) is capable of rapid and accurate cell sorting, it occupies a large volume of the instrument and inherently brings in aerosol generation as well as cross-contamination among samples. The sorting completed in a fully enclosed and disposable microfluidic chip has the potential to eliminate the above concerns. However, current microfluidic cell sorters are hindered by the high complexities of the fabrication procedure and the off-chip setup. In this paper, a spark-cavitation-bubble-based fluorescence-activated cell sorter is developed to perform fast and accurate sorting in a microfluidic chip. It features a simple structure and an easy operation. This microfluidic sorter comprises a positive electrode of platinum and a negative electrode of tungsten, which are placed on the side of the main channel. By applying a high-voltage discharge on the pair of electrodes, a single spark cavitation bubble is created to deflect the target particle into the downstream collection channel. The sorter has a short switching time of 150 μs and a long lifespan of more than 100 million workable actions. In addition, a novel control strategy is proposed to dynamically adjust the discharge time to stabilize the size of the cavitation bubble for continuous sorting. The dynamic control of continuously triggering the sorter, the optimal delay time between fluorescence detection and cell sorting, and a theoretical model to predict the ideal sorting recovery and purity are studied to improve and evaluate the sorter performance. The experiments demonstrate that the sorting rate of target particles achieves 1200 eps, the total analysis throughput is up to 10,000 eps, the particles sorted at 4000 eps exhibit a purity greater than 80% and a recovery rate greater than 90%, and the sorting effect on the viability of HeLa cells is negligible.

Project description:Numerous studies have already shown that the process of cavitation can be successfully used for water treatment and eradication of bacteria. However, most of the relevant studies are being conducted on a macro scale, so the understanding of the processes at a fundamental level remains poor. In attempt to further elucidate the process of cavitation-assisted water treatment on a scale of a single bubble, the present paper numerically addresses interaction between a collapsing microbubble and a nearby compliant structure, that mechanically and structurally resembles a bacterial cell. A fluid-structure interaction methodology is employed, where compressible multiphase flow is considered and the bacterial cell wall is modeled as a multi-layered shell structure. Simulations are performed for two selected model structures, each resembling the main structural features of Gram-negative and Gram-positive bacterial cell envelopes. The contribution of two independent dimensionless geometric parameters is investigated, namely the bubble-cell distance δ and their size ratio ς. Three characteristic modes of bubble collapse dynamics and four modes of spatiotemporal occurrence of peak local stresses in the bacterial cell membrane are identified throughout the parameter space considered. The former range from the development of a weak and thin jet away from the cell to spherical bubble collapses. The results show that local stresses arising from bubble-induced loads can exceed poration thresholds of cell membranes and that bacterial cell damage could be explained solely by mechanical effects in absence of thermal and chemical ones. Based on this, the damage potential of a single microbubble for bacteria eradication is estimated, showing a higher resistance of the Gram-positive model organism to the nearby bubble collapse. Microstreaming is identified as the primary mechanical mechanism of bacterial cell damage, which in certain cases may be enhanced by the occurrence of shock waves during bubble collapse. The results are also discussed in the scope of bacteria eradication by cavitation treatment on a macro scale, where processes of hydrodynamic and ultrasonic cavitation are being employed.

Dataset Information

Nucleus factory on cavitation bubble for amyloid ? fibril.

Publications

Nucleus factory on cavitation bubble for amyloid β fibril.

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