Microscopic mechanisms of sonoporation

Achieving remote and non-invasive molecular delivery to cells is an area of increasing industrial and academic interest. A focus for current research activity involves ultrasound exposure (insonation) in the presence of contrast agent microbubbles, which is known to enhance membrane permeability and lead to molecular uptake from the locale[1]. Under high ultrasound pressures (>0.2MPa), this process (sonoporation) can elicit a number of clinically relevant bioeffects such as direct lysis [1,2] and apoptosis [2-4]. Moreover, promising observations of tumour regression have been demonstrated in murine studies [5,6]. However, whilst speculation regarding the physical mechanisms responsible for membrane permeabilization has been widespread, corroboration has, until very recently [7,8] remained elusive. Here we present further direct observational evidence that illuminates the dynamical processes relating to individual cavitation events near cells and which, we speculate, provides a cogent explanation for previous statistical studies on insonated cell populations using flow cytometry.