A thin-layer model for viscoelastic, stress-relaxation testing of cells using atomic force microscopy: Do cell properties reflect metastatic potential?
A thin-layer model for viscoelastic, stress-relaxation testing of cells using atomic force microscopy: Do cell properties reflect metastatic potential?
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DOI：
10.1529/biophysj.106.083097
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发表时间：
2007-03-01
影响因子：
3.4
通讯作者：
Guilak, Farshid
中科院分区：
文献类型：
--
作者：
Darling, Eric M.;Zauscher, Stefan;Guilak, Farshid
原子力显微镜已迅速成为量化单细胞生物物理特性的宝贵工具。然而，基于原子力显微镜的压痕测试的解释高度依赖于测试配置的适当理论模型的使用。在本研究中，开发了一种用于应力松弛的新型薄层粘弹性模型，以量化不同配置的软骨肉瘤细胞的机械特性，以检验粘弹性特性反映细胞的转移潜力和侵袭性的假设，使用三种特征良好的人类软骨肉瘤细胞系（JJ012、FS090、105KC），这三种细胞系分别显示软骨细胞分化增加和恶性肿瘤减少。在电镀后 2 小时和 2 天进行单细胞应力松弛测试，以确定球形或散布形态的细胞机械性能，并使用新的理论模型进行分析。在这两个时间点，JJ012 细胞在所检查的细胞系中具有最低的模量，而 FS090 通常具有最高的模量。与 2 小时时间点相比，第 2 天时，所有细胞均表现出硬度增加和表观粘度下降。荧光标记显示FS090细胞和JJ012/105KC细胞中扩散细胞中的F-肌动蛋白结构存在显着差异。与之前的研究结果结合起来，这些发现表明细胞转化和致瘤性与细胞模量和表观粘度的降低有关，这表明细胞机械特性可以提供对细胞转移潜力和侵袭性的深入了解。
Atomic force microscopy has rapidly become a valuable tool for quantifying the biophysical properties of single cells. The interpretation of atomic force microscopy-based indentation tests, however, is highly dependent on the use of an appropriate theoretical model of the testing configuration. In this study, a novel, thin-layer viscoelastic model for stress relaxation was developed to quantify the mechanical properties of chondrosarcoma cells in different configurations to examine the hypothesis that viscoelastic properties reflect the metastatic potential and invasiveness of the cell using three well-characterized human chondrosarcoma cell lines (JJ012, FS090, 105KC) that show increasing chondrocytic differentiation and decreasing malignancy, respectively. Single-cell stress relaxation tests were conducted at 2 h and 2 days after plating to determine cell mechanical properties in either spherical or spread morphologies and analyzed using the new theoretical model. At both time points, JJ012 cells had the lowest moduli of the cell lines examined, whereas FS090 typically had the highest. At 2 days, all cells showed an increase in stiffness and a decrease in apparent viscosity compared to the 2-h time point. Fluorescent labeling showed that the F-actin structure in spread cells was significantly different between FS090 cells and JJ012/105KC cells. Taken together with results of previous studies, these findings indicate that cell transformation and tumorigenicity are associated with a decrease in cell modulus and apparent viscosity, suggesting that cell mechanical properties may provide insight into the metastatic potential and invasiveness of a cell.