Combining Optical Tweezers and Quantitative Phase Imaging for Interrogating the Mechanical Properties of Ovarian Cancer Cells and Erythrocyte Derived Microparticles
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Combining Optical Tweezers and Quantitative Phase Imaging for Interrogating the Mechanical Properties of Ovarian Cancer Cells and Erythrocyte Derived Microparticles

  • Author(s): Lu, Thompson
  • Advisor(s): Anvari, Bahman
  • et al.
Abstract

The viscoelastic properties of cell membranes such as cytoskeleton-membrane adhesion, membrane tension, and viscosity all offer valuable insight into fundamental cellular processes such as division, motility, adhesion, and deformability. Cancer cells have significantly increased deformability when compared to their normal counter parts. Erythrocytes circulation life-time is dependent on their ability to deform to pass through narrow passages such as capillaries and spleen. This dissertation examines two different biological systems from a mechanical perspective: Ovarian cancers cells and erythrocyte membrane derived constructs.To perform these studies, I utilize a combined optical tweezers and quantitative phase imaging system to extract and image membrane tethers. From measuring the forces associated with tether extraction, I determine the forces associated with cytoskeleton-membrane adhesion, membrane tension, stiffness, viscosity, and relaxation time constants. By estimating the diameter of membrane tethers, I calculate the bending modulus and tether tension, which are correlated with deformability. In the ovarian cancer cell studies, I investigated and compared viscoelastic properties of a metastatic epithelial ovarian cancer cell line (SKOV3) and normal immortalized ovarian cancer (IOSE364). The results from this study show that SKOV3 cells are less stiff, less viscous, and more deformable than IOSE364 cells. The findings suggest that membrane mechanics play a large role in cancer cell behavior and the cell membrane can also be a target for therapeutics. In the erythrocyte-derived particle studies, I investigate the viscoelastic properties of red blood cells, micron-sized erythrocyte ghosts (µEGs), and micron-sized erythrocyte ghosts loaded with indocyanine green (µNETs). The circulation dynamics and kinetics of micron-sized particles are correlated with their mechanical properties. The results from this study shows that the fabrication of RBCs into EGs drastically decreases the tether stiffness, cytoskeleton membrane adhesion, and increases tether relaxation dynamics, which in turn decreases the deformability compared to red blood cells. The results also show that indocyanine green loading into EGs can restore some mechanical properties similar to red blood cells. The important findings are that the method for preparing erythrocyte membranes as drug delivery construct greatly affects the particles mechanical properties and the cargo loaded into the construct can potentially affect the mechanical properties of the construct.

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