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Mechanical properties of normal versus cancerous breast cells

机译:正常与癌性乳腺癌细胞的机械特性

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摘要

A cell’s mechanical properties are important in determining its adhesion, migration, and response to the mechanical properties of its microenvironment and may help explain behavioral differences between normal and cancerous cells. Using fluorescently labeled peroxisomes as microrheological probes, the interior mechanical properties of normal breast cells were compared to a metastatic breast cell line, MDA-MB-231. To estimate the mechanical properties of cell cytoplasms from the motions of their peroxisomes, it was necessary to reduce the contribution of active cytoskeletal motions to peroxisome motion. This was done by treating the cells with blebbistatin, to inhibit myosin II, or with sodium azide and 2-deoxy-D-glucose, to reduce intracellular ATP. Using either treatment, the peroxisomes exhibited normal diffusion or subdiffusion, and their mean squared displacements (MSDs) showed that the MDA-MB-231 cells were significantly softer than normal cells. For these two cell types, peroxisome MSDs in treated and untreated cells converged at high frequencies, indicating that cytoskeletal structure was not altered by the drug treatment. The MSDs from ATP-depleted cells were analyzed by the generalized Stokes–Einstein relation to estimate the interior viscoelastic modulus G* and its components, the elastic shear modulus G′ and viscous shear modulus G″, at angular frequencies between 0.126 and 628rad/s. These moduli are the material coefficients that enter into stress–strain relations and relaxation times in quantitative mechanical models such as the poroelastic model of the interior regions of cancerous and non-cancerous cells.
机译:细胞的机械性能对于确定其粘附,迁移和对其微环境的机械性能的响应很重要,并且可以帮助解释正常细胞与癌细胞之间的行为差​​异。使用荧光标记的过氧化物酶体作为微流变探针,将正常乳腺细胞的内部机械性能与转移性乳腺细胞系MDA-MB-231进行了比较。为了从它们的过氧化物酶体的运动来估计细胞质的机械特性,有必要减少活性细胞骨架运动对过氧化物酶体运动的贡献。这是通过用blebbistatin处理细胞来抑制肌球蛋白II,或用叠氮化钠和2-deoxy-D-葡萄糖处理以减少细胞内ATP来完成的。无论采用哪种处理方法,过氧化物酶体均表现出正常的扩散或亚扩散,其均方位移(MSD)表明MDA-MB-231细胞明显比正常细胞软。对于这两种细胞类型,处理过的细胞和未处理过的细胞中的过氧化物酶体MSD以高频率会聚,表明药物治疗并未改变细胞骨架结构。通过广义的Stokes-Einstein关系分析了ATP耗尽细胞的MSD,以估计角频率在0.126和628rad / s之间的内部粘弹性模量G *及其成分,即弹性剪切模量G'和粘性剪切模量G''。 。这些模量是在定量力学模型(例如癌细胞和非癌细胞内部区域的多孔弹性模型)中进入应力-应变关系和弛豫时间的材料系数。

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