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Membrane disruption by optically controlled microbubble cavitation

Nature Physics volume 1, pages 107–110 (2005)Cite this article

Abstract

In fluids, pressure-driven cavitation bubbles have a nonlinear response that can lead to extremely high core-energy densities during the collapse phase—a process underpinning phenomena such as sonoluminescence1 and plasma formation2. If cavitation occurs near a rigid surface, the bubbles tend to collapse asymmetrically, often forming fast-moving liquid jets that may create localized surface damage3. As encapsulated microbubbles are commonly used to improve echo generation in diagnostic ultrasound imaging, it is possible that such cavitation could also lead to jet-induced tissue damage. Certainly ultrasonic irradiation (insonation) of cells in the presence of microbubbles can lead to enhanced membrane permeabilization and molecular uptake (sonoporation)4,5,6,7, but, although the mechanism during low-intensity insonation is clear8, experimental corroboration for higher pressure regimes has remained elusive. Here we show direct observational evidence that illuminates the energetic micrometre-scale interactions between individual cells and violently cavitating shelled microbubbles. Our data suggest that sonoporation at higher intensities may arise through a synergistic interplay involving several distinct processes.

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Figure 1: Apparatus and configuration of the optically trapped microbubble in relation to a coverslip/monolayer system.
Figure 2: Representative UHS sequences acquired at a framing rate of 500 kHz showing microbubble cavitation, in proximity to naked coverslips (a, b) and at cell monolayers (c, d).
Figure 3: Correlation of specific cavitation events with membrane damage.

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References

  1. Hilgenfeldt, S., Grossmann, S. & Lohse, D. A simple explanation of light emission in sonoluminescence. Nature 398, 402–405 (1999).

    Article  ADS  Google Scholar 

  2. Flannigan, D. J. & Suslick, K. S. Plasma formation and temperature measurement during single bubble cavitation. Nature 434, 52–55 (2005).

    Article  ADS  Google Scholar 

  3. Benjamin, T. B. & Ellis, A. T. The collapse of cavitation bubbles and the pressure thereby produced against solid boundaries. Phil. Trans. R. Soc. Lond. A 260, 221–245 (1966).

    Article  ADS  Google Scholar 

  4. Ward, M., Wu, J. & Chiu, J. F. Ultrasound induced cell lysis and sonoporation enhanced by contrast agents. J. Acoust. Soc. Am. 105, 2951–2957 (1999).

    Article  ADS  Google Scholar 

  5. Feril, L. B. et al. Enhancement of ultrasound-induced apoptosis and cell lysis by echo contrast agents. Ultrasound Med. Biol. 29, 331–337 (2003).

    Article  Google Scholar 

  6. Honda, H., Kondo, T., Zhao, Q. L., Feril, L. B. & Kitagawa, H. Role of intracellular calcium ions and reactive oxygen species in apoptosis induced by ultrasound. Ultrasound Med. Biol. 30, 683–692 (2004).

    Article  Google Scholar 

  7. Miller, D. L. & Song, J. Tumour growth reduction and DNA transfer by cavitation-enhanced high intensity focused ultrasound in vivo. Ultrasound Med. Biol. 29, 887–893 (2003).

    Article  Google Scholar 

  8. Marmottant, P. & Hilgenfeldt, S. Controlled vesicle deformation and lysis by single oscillating bubbles. Nature 423, 153–156 (2003).

    Article  ADS  Google Scholar 

  9. Canatella, P. J. & Prausnitz, M. R. Prediction and optimization of gene transfection and drug delivery by electroporation. Gene Therapy 8, 1464–1469 (2001).

    Article  Google Scholar 

  10. Tirlapur, U. K. & König, K. Targeted transfection by femtosecond laser. Nature 418, 290–291 (2002).

    Article  ADS  Google Scholar 

  11. Gahagan, K. T. & Swartzlander, G. A. Trapping of low-index microparticles in an optical vortex. J. Opt. Soc. Am. B 15, 524–534 (1998).

    Article  ADS  Google Scholar 

  12. Phillip, A. & Lauterborn, W. Cavitation erosion by single laser-produced bubbles. J. Fluid Mech. 361, 75–116 (1998).

    Article  ADS  Google Scholar 

  13. Plesset, M. S. & Chapman, R. B. Collapse of an initially spherical vapour cavity in the neighbourhood of a solid boundary. J. Fluid. Mech. 47, 283–290 (1971).

    Article  ADS  Google Scholar 

  14. Ohl, C. D. & Ikink, R. Shock wave induced jetting of micron size bubbles. Phys. Rev. Lett. 90, 214502 (2003).

    Article  ADS  Google Scholar 

  15. Van Wamel, A., Bouakaz, A., Versluis, M. & de Jong, N. Micromanipulation of endothelial cells: Ultrasound-microbubble-cell interactions. Ultrasound Med. Biol. 30, 1255–1258 (2004).

    Article  Google Scholar 

  16. Wolfram, B., Mettin, R., Kurz, T. & Lauterborn, W. Observations of pressure wave excited contrast agent microbubbles in the vicinity of cells. Appl. Phys. Lett. 81, 5060–5062 (2002).

    Article  ADS  Google Scholar 

  17. Postema, M., Van Wamel, A., Lancée, C. T. & de Jong, N. Ultrasound-induced encapsulated microbubble phenomena. Ultrasound Med. Biol. 30, 827–840 (2004).

    Article  Google Scholar 

  18. Postema, M. Medical Bubbles (Universal, Veenedaal, Netherlands, 2004).

    Google Scholar 

  19. Weaver, J. C. & Chizmadzev, Y. A. Theory of electroporation: A review. Bioelectrochem. Bioenerget. 41, 135–160 (1996).

    Article  Google Scholar 

  20. Steinhardt, R. A., Bi, G. & Alderton, J. M. Cell membrane resealing by a vesicular mechanism similar to neurotransmitter release. Science 263, 390–393 (1994).

    Article  ADS  Google Scholar 

  21. Deng, C. X., Sieling, F., Pan, H. & Cui, J. Ultrasound induced cell membrane porosity. Ultrasound Med. Biol. 30, 519–526 (2004).

    Article  Google Scholar 

  22. Guzman, H. R., Nguyen, D. X., Khan, S. & Prausnitz, M. R. Ultrasound-mediated disruption of cell membranes. II. Heterogeneous effects on cells. J. Acoust. Soc. Am. 110, 597–606 (2001).

    Article  ADS  Google Scholar 

  23. Boal, D. Mechanics of the Cell (Cambridge Univ. Press, Cambridge, 2002).

    Google Scholar 

  24. Rotch, C., Jacobson, K. & Radmacher, M. Dimensional and mechanical dynamics of active and stable edges in motile fibroblasts investigated using atomic force microscopy. Proc. Natl Acad. Sci. USA 96, 921–926 (1999).

    Article  ADS  Google Scholar 

  25. Brujan, E. A. The role of cavitation microjets in the therapeutic applications of ultrasound. Ultrasound Med. Biol. 30, 381–387 (2004).

    Article  Google Scholar 

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Acknowledgements

We thank the EPSRC, SHEFC and National Institutes for Health for financial support and the EPSRC equipment loan pool (A. Walker and P. Anthony) for use of the high-speed imaging systems. We also gratefully acknowledge advice and assistance from V. Zarnitzyn and M. Postema (sonoporation), D. McLean (technical construction), M. McDonald (optical trapping) and J. Christophe Bourdon and P. Robertson (cell culture).

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Authors and Affiliations

  1. Department of Surgery and Molecular Oncology, Institute of Medical Science and Technology, Ninewells Hospital, University of Dundee, Dundee, DD1 9SY, Scotland, UK

    Paul Prentice, Alfred Cuschieri & Paul Campbell

  2. School of Physics and Astronomy, University of St Andrews, North Haugh, St Andrews KY16 9SS, Fife, Scotland, UK

    Kishan Dholakia

  3. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, Georgia, 30332-0100, USA

    Mark Prausnitz

  4. Div. Electronic Engineering and Physics, University of Dundee, Dundee, DD1 4HN, Scotland, UK

    Paul Campbell

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  1. Paul Prentice
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Correspondence to Paul Campbell.

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M. R. P. is on the advisory board of Cytodome. The rest of the authors declare that they have no competing financial interests.

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Prentice, P., Cuschieri, A., Dholakia, K. et al. Membrane disruption by optically controlled microbubble cavitation. Nature Phys 1, 107–110 (2005). https://doi.org/10.1038/nphys148

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