SUMMARY

Mechanical forces are involved in a variety of cellular functions and are mediated by cellular structures, such as the dynamic cytoskeleton network. Abnormalities in mechanical stiffness often accompany cellular dysfunction through changes in cytoskeleton structure, as occurs in diseases such as cancers. As one of the leading lethal cancers in the US, ovarian cancer is difficult to detect due to lack of reliable biomarkers, novel and effective biomarkers are needed to complement the existing methods of detection. In this research, we investigated cell stiffness as a biomarker in ovarian cancer for the purpose of early cancer detection and grading metastatic potential. The mechanical heterogeneity of single cell is also studied. Atomic force microscopy is used to determine mechanical properties of ovarian single cells from healthy and cancerous phenotypes. We found that cancerous cells are softer than noncancerous ones, and more invasive cells are significantly softer. As a partial explanation of this phenomenon, a quantitative study was conducted and showed that cells of higher metastatic potential display more irregular actin cytoskeleton structures. Complicating the understanding of cellular mechanics is the nonlinearity inherent in many biological materials. Mechanical nonlinearity of single cells was investigated using an indentation-dependent Hertzian model. We found that the effect of mechanical nonlinearity was significant and needs to be examined in the determination of cell stiffness. In addition, mapping of elasticity of single cells showed that mechanical heterogeneity is consistent with intracellular structural heterogeneity, with the nucleus is softer than the surrounding cytoplasm. Cell stiffness showed a dependence on cell cycle in the healthy phenotype. The change of stiffness due to malignance in ovarian cells may provide a convenient way to diagnose ovarian cancer, particularly in discriminating invasive cancer from noninvasive cancer.