Response of Single Cells to Shock Waves and Numerically Optimized Waveforms for Cancer Therapy

Abstract

Shock waves are used clinically for breaking kidney stones and treating musculoskeletal indications. The mechanisms by which shock waves interact with tissue are still not well understood. Here, ultra-high-speed imaging was used to visualize the deformation of individual cells embedded in a tissue-mimicking phantom when subject to shock-wave exposure from a clinical source. Three kidney epithelial cell lines were considered to represent normal healthy (human renal epithelial), cancer (CAKI-2), and virus-transformed (HK-2) cells. The experimental results showed that during the compressive phase of the shock waves, there was a small (<2%) decrease in the projected cell area, but during the tensile phase, there was a relatively large (∼10%) increase in the projected cell area. The experimental observations were captured by a numerical model with a constitutive material framework consisting of an equation of state for the volumetric response and hyper-viscoelasticity for the deviatoric response. To model the volumetric cell response, it was necessary to change from a higher bulk modulus during the compression to a lower bulk modulus during the tensile shock loading. It was discovered that cancer cells showed a smaller deformation but faster response to the shock-wave tensile phase compared to their noncancerous counterparts. Cell viability experiments, however, showed that cancer cells suffered more damage than other cell types. These data suggest that the cell response to shock waves is specific to the type of cell and waveforms that could be tailored to an application. For example, the model predicts that a shock wave with a tensile stress of 4.59 MPa would increase cell membrane permeability for cancer cells with minimal impact on normal cells.