Interrogation of drug effects on HeLa cells by exploiting new AFM mechanical biomarkers
Interrogation of drug effects on HeLa cells by exploiting new AFM mechanical biomarkers
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利用新的 AFM 机械生物标志物探究药物对 HeLa 细胞的作用
DOI：
10.1039/c7ra06233h
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发表时间：
2017-09
期刊：
影响因子：
3.9
通讯作者：
Huabin Wang
中科院分区：
文献类型：
--
作者：
Xiaoling Yun;Mingjie Tang;Zhongbo Yang;Jonathan J. Wilksch;Xiu Peng;Haiyang Gao;Feng Zhang;Huabin Wang
发现了新的机械生物标志物，并用于研究药物对HeLa细胞的影响。在用抗癌药物（多西他赛，微管聚合剂）治疗之前和之后，使用先进的原子力显微镜（AFM）技术测量HeLa细胞，并使用理论模型分析细胞的生物力学性质。生物力学结果表明，未处理的HeLa细胞的表面刷的长度、粘度因子和粘附功分别从920 nm、0.72和4.12 × 10−16 Nm减少到处理后的673 nm、0.52和5.37 × 10−17 Nm。为了揭示这些变化的潜在机制，透射电子显微镜（TEM）和蛋白质印迹分析，以表征细胞的结构变化。与未处理的细胞相比，TEM图像证实了处理的细胞表面上的较薄的刷层，而从细胞中提取的微管蛋白的蛋白质印迹表明处理的细胞的微管浓度增加。这些变化与先前关于多西他赛对细胞影响的研究一致。基于上述结果，我们认为多西紫杉醇可导致HeLa细胞内微管网络增加，细胞表面刷状层变薄，细胞表面刷状层长度、粘度因子和粘附功可作为评价药物作用的有效力学生物标志物。这项工作展示了一种新的基于AFM的技术，可以用来评估药物对细胞的作用，并有望应用于药物筛选。
New mechanical biomarkers were discovered and used to investigate drug effects on HeLa cells. HeLa cells were measured using advanced atomic force microscopy (AFM) techniques before and after treatment with an anticancer drug (docetaxel, a microtubule polymerizer) and the biomechanical properties of cells were analyzed using theoretical models. The biomechanical results show that the length of the surface brush, the factor of viscosity, and the adhesion work of untreated HeLa cells reduced from 920 nm, 0.72 and 4.12 × 10−16 N m to 673 nm, 0.52 and 5.37 × 10−17 N m for treated cells, respectively. In order to reveal the underlying mechanisms of these changes, transmission electron microscopy (TEM) and western blotting assays were employed to characterize structural changes of the cells. Compared to the untreated cells, TEM images confirmed a thinner brush layer on the surface of treated cells while the western blotting of tubulin extracted from the cells indicated an increased microtubule concentration for the treated cells. These changes are consistent with previous studies on the influence of docetaxel on cells. Based on the above results, we conclude that docetaxel can lead to an increased microtubule network in HeLa cells, a thinner brush layer on HeLa cell surfaces and that the length of surface brush, the factor of viscosity, and the adhesion work can be exploited as effective mechanical biomarkers to evaluate drug effects on HeLa cells. This work demonstrates a new AFM-based technique that can be exploited to assess drug action on cells and is promising for the application of drug screening.
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影响因子：
3.5
作者：
Cross, Sarah E.;Jin, Yu-Sheng;Gimzewski, James K.
通讯作者：
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DOI：
10.1021/la701878n
发表时间：
2007-09
期刊：
Langmuir : the ACS journal of surfaces and colloids
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影响因子：
3.9
作者：
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通讯作者：
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影响因子：
5.5
作者：
G. Subramanian;David R M Williams;P. Pincus
通讯作者：
G. Subramanian;David R M Williams;P. Pincus
DOI：
10.1021/acs.langmuir.6b03764
发表时间：
2017-01
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
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作者：
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通讯作者：
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