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

机译:单细胞对冲击波和数值优化波形的响应用于癌症治疗

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摘要

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.
机译:冲击波在临床上用于破坏肾结石和治疗肌肉骨骼适应症。冲击波与组织相互作用的机制仍未得到很好的理解。在这里,当经受来自临床来源的冲击波照射时,超高速成像用于可视化嵌入模仿组织的幻影中的单个细胞的变形。认为三种肾上皮细胞系代表正常健康(人肾上皮),癌症(CAKI-2)和病毒转化(HK-2)细胞。实验结果表明,在冲击波的压缩阶段,预计的单元格面积减少了很小的(<2%),但是在拉伸阶段,预计的单元格面积增加了相对较大的(〜10%)细胞面积。通过具有本构材料框架的数值模型来捕获实验观察结果,该本构材料框架由用于体积响应的状态方程和用于偏斜响应的超粘弹性组成。为了模拟细胞的体积响应,有必要从压缩期间的较高体积模量转变为拉伸冲击载荷期间的较低体积模量。发现与非癌对应物相比,癌细胞显示出较小的变形,但对冲击波拉伸相的响应更快。然而,细胞活力实验表明,癌细胞比其他细胞类型遭受的损害更大。这些数据表明,单元格对冲击波的响应是特定于单元格的类型和可以针对应用定制的波形。例如,该模型预测,张应力为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则最小。

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