Therapeutic ultrasound is widely employed in clinical applications but its mechanism of action remains unclear. Here we report prompt fluidization of a cell and dramatic acceleration of its remodeling dynamics when exposed to low intensity ultrasound. These physical changes are caused by very small strains (10−5) at ultrasonic frequencies (106 Hz), but are closely analogous to those caused by relatively large strains (10−1) at physiological frequencies (100 Hz). Moreover, these changes are reminiscent of rejuvenation and aging phenomena that are well-established in certain soft inert materials. As such, we suggest cytoskeletal fluidization together with resulting acceleration of cytoskeletal remodeling events as a mechanism contributing to the salutary effects of low intensity therapeutic ultrasound.

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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.