Effects of plasma membrane cholesterol content on ultrasound and microbubble mediated sonoporation

Ultrasonically-stimulated microbubbles can increase cell membrane permeability and allow otherwise impermeable molecules to enter the intracellular space of cells; a phenomenon known as sonoporation. In this thesis, the effect of plasma membrane cholesterol content on modulating ultrasound-microbubble induced cell permeabilization and viability was investigated in an in vitro cell suspension model. Breast cancer cells (MDA-MB-231) with modified cholesterol content were exposed to ultrasound and microbubbles at varying acoustic pressures. The effect on cells was assessed through uptake of FITC-dextran (70kDa) and cell viability (propidium iodide marker) using flow cytometry. Ultrasound and microbubble induced permeabilization of cells depended on cholesterol content of the plasma membrane. The highest permeability of ~30% was achieved in unmodified cells compared to ~15% for cholesterol depleted cells at 1.5 MPa peak negative pressure. This study indicated that both addition and removal of cholesterol from cell plasma membrane results in decrease of ultrasound and microbubble induced permeabilization.