The Woodruff School

SUMMARY

Ovarian cancer has one of the highest mortality rates of all the cancers and is difficult to detect at an early stage, therefore, it's necessary to develop new ways to catch cancer early and quantify it's metastasis ability conveniently. Cell is a complex system which interacts with the environments continuously, among it's properties, mechanical stiffness is mainly mediated by cytoskeleton and reveals malignant state of cells. The purpose of this proposal is to study properties of cells related to ovarian cancer and mechanical properties of cells of different states, investigate the relationship between stiffness and other properties of single cells, and try to use stiffness as a biomarker of ovarian cancer and grade metastatic potential. In addition, the effects of cell cycle and heterogeneity on single cell stiffness is also under study.
Atomic force microscopy(AFM) is utilized to determine mechanical properties of single cells of healthy and cancerous phenotypes, actin cytoskeleton is also investigated and related to stiffness. The effect of substrate on stiffness determination, which arises from immobilization of cells on hard substrate during stiffness measurements using AFM, is studied using ultra thin polymer films bonded on hard glass substrate, the point wise Young's modulus as calculated from the point wise Hertz model indicated a power relationship between the onset of substrate effect and film thickness. Based on the study on ultra thin polymer films, the effect of heterogeneity on cell stiffness measurement can be evaluated, which will provide insightful information about the nucleus.
The change of stiffness due to malignance in ovarian cells, as confirmed by the stiffness measurement of healthy and cancerous cells, may provide a convenient way to diagnose ovarian cancer at an early stage. Metastasis potential of various malignant cancer cells is measured and shows a negative correlation with stiffness, which implies that stiffness can potentially be used to grade metastasis for malignant cancer cells.

SUBJECT:	Ph.D. Proposal Presentation

BY:	Wenwei Xu

TIME:	Monday, August 13, 2012, 2:00 p.m.

PLACE:	MRDC Building, 4211

TITLE:	Investigation of Stiffness as a Biomarker in Ovarian Cancer Cells

COMMITTEE:	Dr. Todd Sulchek, Chair (ME) Dr. Alexander Alexeev (ME) Dr. Cheng Zhu (BME) Dr. Wilbur Lam (BME) Dr. John McDonald (BIO)

SUMMARY Ovarian cancer has one of the highest mortality rates of all the cancers and is difficult to detect at an early stage, therefore, it's necessary to develop new ways to catch cancer early and quantify it's metastasis ability conveniently. Cell is a complex system which interacts with the environments continuously, among it's properties, mechanical stiffness is mainly mediated by cytoskeleton and reveals malignant state of cells. The purpose of this proposal is to study properties of cells related to ovarian cancer and mechanical properties of cells of different states, investigate the relationship between stiffness and other properties of single cells, and try to use stiffness as a biomarker of ovarian cancer and grade metastatic potential. In addition, the effects of cell cycle and heterogeneity on single cell stiffness is also under study. Atomic force microscopy(AFM) is utilized to determine mechanical properties of single cells of healthy and cancerous phenotypes, actin cytoskeleton is also investigated and related to stiffness. The effect of substrate on stiffness determination, which arises from immobilization of cells on hard substrate during stiffness measurements using AFM, is studied using ultra thin polymer films bonded on hard glass substrate, the point wise Young's modulus as calculated from the point wise Hertz model indicated a power relationship between the onset of substrate effect and film thickness. Based on the study on ultra thin polymer films, the effect of heterogeneity on cell stiffness measurement can be evaluated, which will provide insightful information about the nucleus. The change of stiffness due to malignance in ovarian cells, as confirmed by the stiffness measurement of healthy and cancerous cells, may provide a convenient way to diagnose ovarian cancer at an early stage. Metastasis potential of various malignant cancer cells is measured and shows a negative correlation with stiffness, which implies that stiffness can potentially be used to grade metastasis for malignant cancer cells.