Mechanical Modeling and Characterization of Cancer Cells Using Optical Tweezers

In this thesis, the development of a novel optical tweezer is described. Additionally, alterations in the mechanical properties of cancer cells associated with metastatic transformation was characterized using this technology. Cell mechanical properties can be utilized as a quantitative measure for understanding the pathophysiological behavior of cells and evaluating pharmacological treatments that modify the cell structure. Thus, an oscillating optical tweezer capable of applying time varying force and manipulating the cell cytoskeleton was developed in order to measure the mechanical properties and structural changes of single epithelial cancer cells and blood cancer cells. Employing this device would be beneficial in differentiating between normal, cancer and metastatic cancer cells and evaluating the effectiveness of different chemotherapeutic approaches. To this end, the developed tool was utilized to conduct a systematic study of the mechanical properties of human epithelial cancer cells by mimicking the condition that causes cancer cell invasiveness and tumour cell transformation. Different signaling pathways that modulate actin organization under hypoxia were studied via analyzing the biophysical properties of cancer cells and quantifying cytoskeleton rearrangement employing the oscillating optical tweezer. It was demonstrated the optical tweezer is a novel, rapid and reliable tool for the identification and characterization of cancer cells and for evaluating therapeutic performance. Finally, a sensitivity study was applied using COMSOL to evaluate the effect of cell-bead geometries on cell mechanical responses for different cell types and optical tweezer experiments