Zhao Xueqin, Zhong Yunxin, Ye Ting, Wang Dajing, Mao Bingwei
College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, 310018, People's Republic of China.
State Key Laboratory of Physical Chemistry of the Solid Surfaces, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, People's Republic of China.
Nanoscale Res Lett. 2015 Dec;10(1):482. doi: 10.1186/s11671-015-1174-y. Epub 2015 Dec 14.
The mechanical properties of cells are considered promising biomarkers for the early diagnosis of cancer. Recently, atomic force microscopy (AFM)-based nanoindentation technology has been utilized for the examination of cell cortex mechanics in order to distinguish malignant cells from normal cells. However, few attempts to evaluate the biomechanical properties of cells have focused on the quantification of the non-homogeneous longitudinal elasticity of cellular structures. In the present study, we applied a variation of the method of Carl and Schillers to investigate the differences between longitudinal elasticity of human cervical squamous carcinoma cells (CaSki) and normal cervical epithelial cells (CRL2614) using AFM. The results reveal a three-layer heterogeneous structure in the probing volume of both cell types studied. CaSki cells exhibited a lower whole-cell stiffness and a softer nuclei zone compared to the normal counterpart cells. Moreover, a better differentiated cytoskeleton was found in the inner cytoplasm/nuclei zone of the normal CRL2614 cells, whereas a deeper cytoskeletal distribution was observed in the probing volume of the cancerous counterparts. The sensitive cortical panel of CaSki cells, with a modulus of 0.350.47 kPa, was located at 237225 nm; in normal cells, the elasticity was 1.201.32 kPa at 113128 nm. The present improved method may be validated using the conventional Hertz-Sneddon method, which is widely reported in the literature. In conclusion, our results enable the quantification of the heterogeneous longitudinal elasticity of cancer cells, in particular the correlation with the corresponding depth. Preliminary results indicate that our method may potentially be applied to improve the detection of cancerous cells and provide insights into the pathophysiology of the disease.
细胞的力学特性被认为是癌症早期诊断的有前景的生物标志物。最近,基于原子力显微镜(AFM)的纳米压痕技术已被用于检测细胞皮层力学,以区分恶性细胞和正常细胞。然而,很少有评估细胞生物力学特性的尝试关注细胞结构非均匀纵向弹性的量化。在本研究中,我们应用了Carl和Schillers方法的一种变体,使用AFM研究人宫颈鳞状癌细胞(CaSki)和正常宫颈上皮细胞(CRL2614)纵向弹性的差异。结果显示,在所研究的两种细胞类型的探测体积中均存在三层异质结构。与正常对应细胞相比,CaSki细胞表现出较低的全细胞硬度和较软的细胞核区域。此外,在正常CRL2614细胞的内细胞质/细胞核区域发现了分化更好的细胞骨架,而在癌性对应细胞的探测体积中观察到更深的细胞骨架分布。CaSki细胞敏感的皮层面板模量为0.350.47 kPa,位于237225 nm处;在正常细胞中,弹性在113128 nm处为1.201.32 kPa。目前改进的方法可以使用文献中广泛报道的传统赫兹-斯内登方法进行验证。总之,我们的结果能够量化癌细胞的非均匀纵向弹性,特别是与相应深度的相关性。初步结果表明,我们的方法可能潜在地应用于改善癌细胞的检测,并为疾病的病理生理学提供见解。