Department of Engineering Science, University of Oxford, Oxford, United Kingdom.
Department of Engineering Science, University of Oxford, Oxford, United Kingdom.
Biophys J. 2018 Mar 27;114(6):1433-1439. doi: 10.1016/j.bpj.2017.09.042.
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.
冲击波在临床上被用于击碎肾结石和治疗肌肉骨骼疾病。但目前人们对于冲击波与组织相互作用的机制仍知之甚少。在此，我们使用超高速成像技术来观察在临床冲击波源照射下，嵌入组织模拟体中的单个细胞的变形。我们选择了三种肾上皮细胞系来分别代表正常健康细胞（人肾上皮细胞）、癌细胞（CAKI-2）和病毒转化细胞（HK-2）。实验结果表明，在冲击波的压缩阶段，细胞的投影面积会略有缩小（<2%），但在拉伸阶段，细胞的投影面积会显著增大（∼10%）。实验观察结果通过一个数值模型进行了捕获，该模型的本构材料框架由一个用于体积响应的状态方程和一个用于偏应变响应的超弹性组成。为了模拟细胞的体积响应，需要在压缩阶段将较高的体积模量转变为拉伸阶段的较低体积模量。研究发现，与非癌细胞相比，癌细胞的变形较小，但对冲击波拉伸阶段的响应更快。然而，细胞活力实验表明，癌细胞比其他细胞类型遭受的损伤更大。这些数据表明，细胞对冲击波的响应取决于细胞类型和波形，这些特性可以根据应用需求进行调整。例如，该模型预测，拉伸应力为 4.59 MPa 的冲击波将增加癌细胞的细胞膜通透性，而对正常细胞的影响最小。
