Understanding cancer cell mechanics allows for the identification of novel disease mechanisms, diagnostic biomarkers, and targeted therapies. In this study, we utilized our previously established fluid shear stress assay to investigate and compare the viscoelastic properties of normal immortalized human astrocytes and invasive human glioblastoma (GBM) cells when subjected to physiological levels of shear stress that are present in the brain microenvironment. We used a parallel-flow microfluidic shear system and a camera-coupled optical microscope to expose single cells to fluid shear stress and monitor the resulting deformation in real time, respectively. From the video-rate imaging, we fed cell deformation information from digital image correlation into a three-parameter generalized Maxwell model to quantify the nuclear and cytoplasmic viscoelastic properties of single cells. We further quantified actin cytoskeleton density and alignment in immortalized human astrocytes and GBM cells via fluorescence microscopy and image analysis techniques. Results from our study show that contrary to the behavior of many extracranial cells, normal and cancerous brain cells do not exhibit significant differences in their viscoelastic properties. Moreover, we also found that the viscoelastic properties of the nucleus and cytoplasm as well as the actin cytoskeletal densities of both brain cell types are similar. Our work suggests that malignant GBM cells exhibit unique mechanical behaviors not seen in other cancer cell types. These results warrant future studies to elucidate the distinct biophysical characteristics of the brain and reveal novel mechanical attributes of GBM and other primary brain tumors.

中文翻译：

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单细胞机械分析揭示了正常脑细胞和肿瘤脑细胞的粘弹性相似性


了解癌细胞机制可以识别新的疾病机制、诊断生物标志物和靶向治疗。在这项研究中，我们利用之前建立的流体剪切应力测定法来研究和比较正常永生化人类星形胶质细胞和侵袭性人类胶质母细胞瘤（GBM）细胞在受到大脑微环境中存在的生理水平的剪切应力时的粘弹性特性。我们使用平行流微流体剪切系统和相机耦合光学显微镜分别将单细胞暴露于流体剪切应力并实时监测由此产生的变形。通过视频速率成像，我们将数字图像相关的细胞变形信息输入三参数广义麦克斯韦模型，以量化单个细胞的核和细胞质粘弹性特性。我们通过荧光显微镜和图像分析技术进一步量化了永生化人星形胶质细胞和 GBM 细胞中的肌动蛋白细胞骨架密度和排列。我们的研究结果表明，与许多颅外细胞的行为相反，正常脑细胞和癌性脑细胞的粘弹性特性没有表现出显着差异。此外，我们还发现两种脑细胞类型的细胞核和细胞质的粘弹性以及肌动蛋白细胞骨架密度相似。我们的工作表明，恶性 GBM 细胞表现出其他癌细胞类型中未见的独特机械行为。这些结果保证了未来的研究能够阐明大脑独特的生物物理特征，并揭示 GBM 和其他原发性脑肿瘤的新机械属性。