Measuring nanoscale viscoelastic parameters of cells directly from AFM force-displacement curves.
Measuring nanoscale viscoelastic parameters of cells directly from AFM force-displacement curves.
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DOI：
10.1038/s41598-017-01784-3
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发表时间：
2017-05-08
影响因子：
4.6
通讯作者：
Raman A
中科院分区：
文献类型：
--
作者：
Efremov YM;Wang WH;Hardy SD;Geahlen RL;Raman A
力-位移(F-Z)曲线是最常用的原子力显微镜(AFM)模式，用于测量活细胞等软材料的局部纳米级弹性特性。然而，一直缺乏一个理论框架来允许对F-Z数据进行后处理来提取其粘弹性本构参数。在这里，我们提出了一种新的方法，可以直接从传统的AFM F-Z实验中提取活细胞和水凝胶等软样品的纳米级粘弹性属性，从而为分析具有任意线性本构关系的细胞弹性和粘弹性属性创建了一个通用平台。基于弹性-粘弹性对应原理的方法在有限元模拟中得到验证，并与现有的活细胞和水凝胶原子力显微镜技术进行了比较。该方法还允许区分哪种粘弹性松弛模型，例如标准线性固体(SLS)和幂定律流变学(PLR)最适合实验数据。将该方法用于提取乳腺癌细胞系(NIH 3T3成纤维细胞、NMuMG上皮细胞、MDA-MB-231和MCF-7乳腺癌细胞)的粘弹性。最后，我们研究了与肿瘤发生相关的粘弹性性质的变化，包括转化生长因子-β诱导的NMuMG细胞上皮向间充质转化和Syk表达诱导的MDAMB-231细胞的表型改变。
Force-displacement (F-Z) curves are the most commonly used Atomic Force Microscopy (AFM) mode to measure the local, nanoscale elastic properties of soft materials like living cells. Yet a theoretical framework has been lacking that allows the post-processing of F-Z data to extract their viscoelastic constitutive parameters. Here, we propose a new method to extract nanoscale viscoelastic properties of soft samples like living cells and hydrogels directly from conventional AFM F-Z experiments, thereby creating a common platform for the analysis of cell elastic and viscoelastic properties with arbitrary linear constitutive relations. The method based on the elastic-viscoelastic correspondence principle was validated using finite element (FE) simulations and by comparison with the existed AFM techniques on living cells and hydrogels. The method also allows a discrimination of which viscoelastic relaxation model, for example, standard linear solid (SLS) or power-law rheology (PLR), best suits the experimental data. The method was used to extract the viscoelastic properties of benign and cancerous cell lines (NIH 3T3 fibroblasts, NMuMG epithelial, MDA-MB-231 and MCF-7 breast cancer cells). Finally, we studied the changes in viscoelastic properties related to tumorigenesis including TGF-β induced epithelial-to-mesenchymal transition on NMuMG cells and Syk expression induced phenotype changes in MDA-MB-231 cells.