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Cell membrane deformation and bioeffects produced by tandem bubble-induced jetting flow.

ABSTRACT: Cavitation with bubble-bubble interaction is a fundamental feature in therapeutic ultrasound. However, the causal relationships between bubble dynamics, associated flow motion, cell deformation, and resultant bioeffects are not well elucidated. Here, we report an experimental system for tandem bubble (TB; maximum diameter = 50 ± 2 ?m) generation, jet formation, and subsequent interaction with single HeLa cells patterned on fibronectin-coated islands (32 × 32 ?m) in a microfluidic chip. We have demonstrated that pinpoint membrane poration can be produced at the leading edge of the HeLa cell in standoff distance Sd ? 30 ?m, driven by the transient shear stress associated with TB-induced jetting flow. The cell membrane deformation associated with a maximum strain rate on the order of 10(4) s(-1) was heterogeneous. The maximum area strain ([Formula: see text]) decreased exponentially with Sd (also influenced by adhesion pattern), a feature that allows us to create distinctly different treatment outcome (i.e., necrosis, repairable poration, or nonporation) in individual cells. More importantly, our results suggest that membrane poration and cell survival are better correlated with area strain integral ([Formula: see text]) instead of [Formula: see text], which is characteristic of the response of materials under high strain-rate loadings. For 50% cell survival the corresponding area strain integral was found to vary in the range of 56 ? 123 ?s with [Formula: see text] in the range of 57 ? 87%. Finally, significant variations in individual cell's response were observed at the same Sd, indicating the potential for using this method to probe mechanotransduction at the single cell level.

SUBMITTER: Yuan F

PROVIDER: S-EPMC4697429 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Cell membrane deformation and bioeffects produced by tandem bubble-induced jetting flow.

Yuan Fang F Yang Chen C Zhong Pei P

Proceedings of the National Academy of Sciences of the United States of America 20151209 51

Cavitation with bubble-bubble interaction is a fundamental feature in therapeutic ultrasound. However, the causal relationships between bubble dynamics, associated flow motion, cell deformation, and resultant bioeffects are not well elucidated. Here, we report an experimental system for tandem bubble (TB; maximum diameter = 50 ± 2 μm) generation, jet formation, and subsequent interaction with single HeLa cells patterned on fibronectin-coated islands (32 × 32 μm) in a microfluidic chip. We have d ...[more]

PMID: 26663913

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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.

Dataset Information

Cell membrane deformation and bioeffects produced by tandem bubble-induced jetting flow.

Publications

Cell membrane deformation and bioeffects produced by tandem bubble-induced jetting flow.

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