Ultrasound induced strain cytoskeleton rearrangement: An experimental and simulation study

Cytoskeleton and specially actin filaments are responsible for mechanical modulation of cellular behavior. These structures could be fluidized in response to transient mechanical cues. Ultrasound devices have been widely used in medicine which their generated ultrasonic waves could disrupt/fluidize actin filaments in cytoskeleton and thus could affect cellular organization. Present research aims at revealing the mechanism of fluidization caused by ultrasound induced strains. First, a numerical simulation was performed to reveal the effect of oscillating ultrasonic pressure on induced deformation in the cell with respect to different cell geometries and exposure conditions. The model revealed that higher pressure and frequencies induce higher levels of strain in the cell. The results also showed that spread cells are more exposed to cytomechanical remodeling due to higher level of ultrasound induced deformations but also the effect of harmonic excitation decreases with spreading. Furthermore, strain values found to be less in the nucleus comparing the value in the cytoplasm, but still these strains can affect the behavior of the cell through mechanotransduction mechanisms. Then, different experimental ultrasound protocols were used to evaluate their effects on cell viability and actin cytoskeleton distribution. Results of Live/Dead assay indicated that high pressure and duration of the exposure had negative effects on the viability of C2C12 cells, while the viability ratio still remained above 85%. In addition, actin fluorescent staining showed that high levels of filament disruption could occur with increasing the pressure. The results of this study shed light on cellular response to mechanical stimuli applied by ultrasonic waves.