Discrimination Between Cervical Cancer Cells and Normal Cervical Cells Based on Longitudinal Elasticity Using Atomic Force Microscopy.

Xueqin Zhao,Dajing Wang,Yunxin Zhong,Ting Ye,Bingwei Mao

doi:10.1186/s11671-015-1174-y

Abstract

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 0.35~0.47 kPa, was located at 237~225 nm; in normal cells, the elasticity was 1.20~1.32 kPa at 113~128 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s11671-015-1174-y) contains supplementary material, which is available to authorized users.

Highlights

IntroductionTumorigenesis and oncogenic progression cause biological and functional alterations and result in mechanical and structural abnormalities in cells
Cancer is currently one of the leading causes of death worldwide
Heterogeneous structures were found to be highly localized in the three cell panels, in the probing volume of both cell types studied

Summary

Introduction

Tumorigenesis and oncogenic progression cause biological and functional alterations and result in mechanical and structural abnormalities in cells. Pathophysiology studies suggest that the etiology of many human diseases is related to deviation from the normal structural and mechanical properties of cells, as. A variety of techniques, such as atomic force microscopy (AFM), optical magnetic twisting cytometry, laser-tracking microrheology, optical tweezers, and micropipette aspiration, have been used to probe the mechanical properties of normal and malignant cells [6,7,8]. A comparison of the mechanical properties reveals that cancerous cells and tissue isolated from cancer patients are softer and more deformed [13,14,15]. In order to examine these mechanical properties, the relative Young’s modulus is typically determined for indentation depths within the range of 200–400 nm, which encompasses the cell cortex (the 50–100-nm-thick zone below the plasma membrane)

Methods

Results

Conclusion