Quantifying Cell-to-Cell Variation in Power-Law Rheology
Quantifying Cell-to-Cell Variation in Power-Law Rheology
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DOI：
10.1016/j.bpj.2013.07.035
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发表时间：
2013-09-03
影响因子：
3.4
通讯作者：
Okajima, Takaharu
中科院分区：
文献类型：
--
作者：
Cai, PingGen;Mizutani, Yusuke;Okajima, Takaharu
在同一来源和类型的单个细胞中，复杂的剪切模数G*呈现出大的对数正态分布，这是空间、时间和内在变化的结果。如此大的分布使药物治疗的统计评估和不同细胞状态的比较变得复杂。然而，人们对细胞间变异的特征知之甚少。在这项研究中，我们研究了这种变异是如何依赖于细胞内的空间位置和肌动蛋白细丝细胞骨架的，肌动蛋白细丝细胞骨架的组织强烈影响细胞力学。通过原子力显微镜对排列在微阵列上的成纤维细胞进行机械探测，我们观察到在肌动蛋白细丝解聚的细胞中，G*的标准偏差sigma显著降低。参数西格玛也表现出亚细胞的空间依赖性。基于我们关于存储模数G‘的sigma的频率依赖性的发现，我们根据细胞变形的软玻璃流变学模型，提出了G’中两种类型的细胞间变化，这两种变化是由纯弹性成分和频率相关成分引起的。我们的结论是，后一种固有的细胞间差异可以通过破坏肌动蛋白网络、探测远离细胞中心的细胞核边界内的位置以及在高负载频率下进行测量来大大减少。
Among individual cells of the same source and type, the complex shear modulus G* exhibits a large log-normal distribution that is the result of spatial, temporal, and intrinsic variations. Such large distributions complicate the statistical evaluation of pharmacological treatments and the comparison of different cell states. However, little is known about the characteristic features of cell-to-cell variation. In this study, we investigated how this variation depends on the spatial location within the cell and on the actin filament cytoskeleton, the organization of which strongly influences cell mechanics. By mechanically probing fibroblasts arranged on a microarray, via atomic force microscopy, we observed that the standard deviation sigma of G* was significantly reduced among cells in which actin filaments were depolymerized. The parameter sigma also exhibited a subcellular spatial dependence. Based on our findings regarding the frequency dependence of sigma of the storage modulus G', we proposed two types of cell-to-cell variation in G' that arise from the purely elastic and the frequency-dependent components in terms of the soft glassy rheology model of cell deformability. We concluded that the latter inherent cell-to-cell variation can be reduced greatly by disrupting actin networks, by probing at locations within the cell nucleus boundaries distant from the cell center, and by measuring at high loading frequencies.