Identifying and controlling acoustic bioeffects.

Abstract

Ultrasound exposure causes internalization of a wide variety of molecules in cells and tissues, especially in the presence of acoustic cavitation. However, high levels of uptake are often accompanied by cell death. This study first analyzed intracellular uptake and cell viability after exposure of porcine carotid arteries to ultrasound ex vivo by confocal microscopy and found that at moderate ultrasound pressure, there was extensive uptake by endothelial cells with little uptake by underlying smooth muscle cells, whereas at high ultrasound pressure there was extensive endothelial cell death and increase uptake by smooth muscle cells. To understand the mechanisms involved in cell uptake and death, sonicated DU145 cells were analyzed by high level microscopy, flow cytometry, and chemical analyses. This work showed that uptake was caused by transient wounds created in the cell membrane that resealed within minutes after sonication. It also identified and quantified seven different cellular responses to this wounding, including cell repair modes and four different death modes. To save cells from apoptotic death, which was found to be mediated by calcium, cells were exposed to a calcium chelator, which rescued approximately half of the apoptotic cells from death.