Study of sonoporation at the single cell level and cellular bioeffects associated with sonoporation facilitated by microbubbles.

Abstract

The interaction of ultrasound-driven microbubbles with cells results in multifaceted cellular bioeffects including physical disruption of cell plasma membrane and subsequent downstream effects. Microbubble facilitated sonoporation, the ultrasound-induced disruption of plasma membrane, enhances the transport of ions, other intracellular contents, and external agents through the membrane into the cytoplasm via diffusion, thereby making it useful for intracellular drug and gene delivery. Transport of these entities, which depends on the dynamic process of pore formation and resealing, plays important roles in many downstream cellular effects of sonoporation beyond the initial pore formation and subsequent diffusion-related transport. For example, extracellular calcium ions diffused into the cytoplasm initiate the process of membrane resealing. In addition, intracellular calcium transients are generated which may be related to many cellular processes triggered by the important second messenger molecule. Recent results of sonoporation at the single cell level and related bioeffects will be discussed. Electrophysiological techniques reveal the dynamic process of sonoporation. Real-time fluorescence imaging measurements of intracellular calcium concentration in mammalian cells subjected to sonoporation demonstrate the spatiotemporal evolution of sonoporation related calcium transients including the large influx of calcium in sonoporated cells and the complex dynamic calcium oscillations and waves. [Work supported by NIH.]