Low Intensity Therapeutic Ultrasound Effect on Nano-Particle Motion in a Viscous Medium

While low intensity therapeutic ultrasound irradiation (LITUS) has been shown to have biological effects on tissue and cells, the physical mechanism leading to those effects has yet to be characterized. As a model system to study effects of LITUS on intracellular organelles, we monitor the dynamics of nanoparticles suspended in a viscoelastic medium, before and during LITUS treatment. Particle motion dynamics can indicate: i) forces acting on similarly-sized intracellular organelles; ii) streaming flow induced in cells and in cavities in contact with cells; and iii) instantaneous (under LITUS) changes in the mechanical properties of viscoelastic media in general and cells in particular. Forces and flow can result in shear stresses that act on the cell membrane of, e.g., endothelial cells in blood vessels and may cause biophysical responses. Particle motion in a high-viscosity, viscoelastic model solution, methyl cellulose, was used as an indicator for sample response under LITUS. The ultrasound-induced motion of nano-particles was quantified by real-time particle-tracking microrheology methods. Particle motion without LITUS irradiation demonstrated diffusive-like behavior with no underlying convection. In contrast, during LITUS irradiation convective motion with a particle-velocity profile parabolic in time was observed. Particles were accelerated after initiation of LITUS irradiation, then a transient phase of constant velocity was observed, and finally the speed was reduced. Altogether the results of the study indicate that LITUS may apply considerable direct forces on suspended particles, a model system for cellular organelles. More studying will help elucidate the mechanisms of LITUS effects. Extending this approach to cells in vitro and evaluating their response can promote the use of ultrasound as a therapeutic tool for delicate manipulation of cells in vivo in a controlled, targeted, and non-invasive way. At the same time, one can define the safety limits and optimal range for therapeutic and diagnostic ultrasound by indicating the threshold for irreversible intracellular changes.