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.