Title page for ETD etd-05182011-152552


Type of Document Master's Thesis
Author Ketene, Alperen Nurullah
URN etd-05182011-152552
Title The AFM Study of Ovarian Cell Structural Mechanics in the Progression of Cancer
Degree Master of Science
Department Mechanical Engineering
Advisory Committee
Advisor Name Title
Agah, Masoud Committee Chair
Behkam, Bahareh Committee Member
Schmelz, Eva M. Committee Member
Keywords
  • Ovarian Cancer
  • Viscoelasticity
  • Hertz Contact Theory
  • Biomechanics
  • Atomic Force Microscopy
  • Cytoskeleton
Date of Defense 2011-05-06
Availability unrestricted
Abstract
According to the American Cancer Society, Cancer is the second most common cause of death in the United States, only exceeded by heart disease. Over the past decade, deciphering the complex structure of individual cells and understanding the symptoms of cancer disease has been a highly emphasized research area. The exact cause of Cancer and the genetic heterogeneity that determines the severity of the disease and its response to treatment has been a great challenge. Researchers from the engineering discipline have increasingly made use of recent technological innovations, namely the Atomic Force Microscope (AFM), to better understand cell physics and provide a means for cell biomechanical profiling.

The presented work’s research objective is to establish a fundamental framework for the development of novel biosensors for cell separation and disease diagnosis. By using AFM nanoindentation, several studies were conducted to identify key distinctions in the trends of cell viscoelasticity between healthy, nontumorigenic cells and their malignant, highly tumorigenic counterparts. The possibility of identifying useful “biomarkers” was also investigated. Due to the lack of an available human ovarian cell line, experiments were done on a recently developed mouse ovarian surface epithelial (MOSE) cell line, which resembles to human cell characteristics and represents early, intermediate, and late stages of the ovarian cancer. Material properties were extracted via Hertz model contact theory.

The experimental results illustrate that the elasticity of late stage MOSE cells were 50% less than that of the early stage. Cell viscosity also decreased by 65% from early to late stage, indicating that the increase in cell deformability directly correlates with increasing levels of malignancy. Various cancer treatment and component-specific drugs were used to identify the causes for the changes in cell biomechanical behavior, depicting that the decrease in the concentration levels of cell structural components, predominantly the actin filament framework, is directly associated with the changes in cell biomechanical property. The investigation of MOSE cells being subject to multiple mechanical loads illustrated that healthy cells react to shear forces by stiffening up to 25% of their original state. On the other hand, cancerous cells are void of such response and at times show signs of decreasing rigidity. Finally, deformation studies on MOSE cancer stem cells have shown that these cells carry a unique elasticity profile among other cell stage phenotypes that could allow for their detection. The results herein carry great potential into contributing to cell separation methods and analysis, furthering the understanding of cell mechanism dynamics.

While prior literature emphasizes on the elastic modulus of cells, the study of cell viscosity and other key material properties holds a critical place in the realistic modeling of these complex microstructures. A comprehensive study of individual cells holds a great amount of promise in the development of effective clinical research in the fight against cancer.

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