Membrane disruption by optically controlled microbubble cavitation

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 sonoluminescence(1) and plasma formation(2). If cavitation occurs near a rigid surface, the bubbles tend to collapse asymmetrically, often forming fast-moving liquid jets that may create localized surface damage(3). 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)(4-7), but, although the mechanism during low-intensity insonation is clear(8), 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.