Ovarian cancer has become the most lethal of gynecological diseases as metastatic potentials with high incidence. The progression of tumor cells is accompanied with the alterations in cellular surface micro-nano structure. The characteristics of cellular surface structures and function in different states could be probed in micro-nano scale using atomic force microscopy (AFM) at single living cell. In this study, we compared the cell surface morphology and plasma membrane roughness of different ovarian cell lines, including normal cell lines HOSEpiC and cancerous cell lines HO-8910. The results show that ovarian cancerous cells HO-8910 exhibit multiple-angle or other irregular shape, while normal cells HOSEpiC have an elliptical or a long spindle-like shape. Ovarian cancerous cells show more disordered actin cytoskeleton structure with increased roughness compare to normal cells, indicating that the roughness of cell surface can be an effective indicator to differentiate the disease state of cells. The micro-nanostructure of cell surface can provide an index for the procession or state of tumor development at single cell level.
Tumor progression and metastasis are often accompanied by the changes in the biomechanical properties of tumor tissues. In this study, the relationship between the pathological classification of different prostate tumor tissues and their biomechanical properties was investigated by atomic force microscopy. The results showed that higher pathological grade of prostate tumor tissues had lower elasticity and viscosity. Compared with traditional pathological analysis, the biomechanical characteristics of tumor tissues obtained by atomic force microscopy could offer a new index for fast clinic diagnosis and differentiation of tumor tissue. It can be used to assist in the assessment of Gleason scores of the gold standard for prostate cancer grading for radical prostatectomy.
Cellular mechanical properties are an important indicator for assessing and analyzing the functions of cells. However, the structure and compositions of the cell are complex. In order to analyze the effects of different components on the mechanical properties of cells, a multi-structured 3D model of cancer cells considering the cytoskeleton, cytoplasm, nucleus and cell membrane was established by finite element method. And the tensegrity structure-finding algorithm was used to analyze the cytoskeletal distribution and the pre-stress of each component. First, the model was verified by comparing numerical results with force-indentation curve obtained by atomic force microscopy in Ho-8910 cells. Then, the elasticity modulus of cell were obtained via applying a load to the established model.Computational simulation showed that cytoskeleton are the major component targeted in resisting compression.In addition, this model can provide useful guidance for the measurement and analysis of single cell through atomic force microscopy.
Prostate cancer is one of the most common malignant tumors threatening male health. The important reason for high mortality rate of prostate cancer is the difficulty in early diagnosis. The nano-mechanical property of cells has been used as a useful index for early cancer diagnosis at single cell level. In this study, atomic force microscopy (AFM) was implemented to measure and compare the morphology and elasticity of different prostate cell lines, including normal cells (PZ-HPV-7) and cancer cells (PC-3). The results showed that the morphology of PZ-HPV-7 cell has a multiple-angle or other irregular shape and the cellular surface is smooth with fewer protrusions. While PC-3 cell has a spindle or spherical shape with more protrusions on the membrane. The average values of elasticity of PZ-HPV-7 and PC-3 cells were 2206.85±1084.99 Pa and 1226.19±520.36 Pa, respectively. And the average values of viscosity were 20.21 ± 4.96 Pa.s and 13.24 ± 4.52 Pa.s, respectively. We found that the elasticity and viscosity of PC-3 were significantly lower than those of PZ-HPV-7, suggesting that the prostate cancer cells are softer than the normal counterpart. It shows that the nanomechanical properties of cells may provide an early index at single cell level for prostate cancer early detection.
Ovarian cancer has become one of the most common malignant tumors threatening female genital health. Recently, biomechanical properties of single cell have been reported as a potential index for early cancer detection. In this study, the viscoelastic properties of ovarian cancer cells were determined using stress-relaxation approach by atomic force microscopy (AFM). Individual force-time curves were recorded at maximum loads of 0.5, 1 and 2 nN, and the stressrelaxation time was 2 s for all the stress-relaxation measurements. A theoretical method of stress relaxation was proposed and the viscoelasticity of the cells was obtained according to a linear solid model. The results showed that the values of average viscosity of ovarian cancer cells were respectively 54.0±6.5 Pa-s, 100.5±13.2 Pa-s and 113.6±13.2 Pa-s using the three different loading forces from 0.5 nN to 2 nN. Furthermore, the values of average elasticity modulus were respectively 657.0±69.9 Pa, 730.9±67.0 Pa, 895.0±71.3 Pa. In conclusion, the viscoelasticity properties of the cells increased as the loading force increased from 0.5 nN to 2 nN. Our study indicates that the viscoelasticity of the ovarian cancer cells can be acquired by stress-relaxation approach and the loading force is an important factor that can affect the cellular viscoelasticity. It will shed new light on cancer early detection based on cellular viscoelasticity index at single cell level.
In this study, HOSEpiC ovarian cell was cultured on hydrogel substrates with three different Young moduli of 3, 19 and 35 kPa. Atomic force microscopy was used to measure the elasticity of cells on three different stiffness substrates. Furthermore, the distribution of actin filaments in HOSEpiC cell was observed by confocal imaging. From the measurements of atomic force microscopy, we found that substrate stiffness would cause changes of cellular elasticity. The largest one was on the substrate of 35 kPa, followed by the 19 kPa and cells on 3 kPa was the smallest. Besides, from the confocal imaging, it could be observed that the distribution of actin filaments in the cells was different on the three substrates. All these results showed that the elasticity of the cells was lower on the substrates with smaller stiffness, which indicated that cells appeared softer when the stiffness of substrate decreased.