The Impacts of Microbubble-Induced Sonoporation on Cell Membrane Permeability and Cytoskeleton Arrangement

Abstract

Microbubble-mediated sonoporation has shown its great potential in facilitating intracellular uptake of gene/drugs and other therapeutic agents. However, the biophysical mechanisms underlying cell-bubble interactions remain unclear. Particularly, the cell cycle-phase-dependent cellular responses to sonoporation have never been reported. Here, efficient synchronizations were performed to arrest HeLa cells in individual cycle phases. Then, atomic force microscopy was adopted to examine the topography and stiffness of synchronized cells. Finally, real-time fluorescence imaging system was designed to simultaneously visualize sonoporation-induced variations in cell membrane permeabilization and cytoskeleton arrangement. The results showed that G1-phase cells had the largest height and elastic modulus, while S-phase cells were the flattest and softest ones. Consequently, S-Phase might become the preferred cycle for sonoporation treatment, due to the greatest enhancement of membrane permeability and the fastest cytoskeleton disassembly. These findings may benefit ongoing efforts pursuing rational utilization of microbubble-mediated sonoporation in cell-cycle-targeted gene/drug delivery for cancer therapy.