Investigating the Mechanics of Cancer Cell Membranes Using Microfluidics

Open Access
Author:
Ramadi, Khalil Basil
Area of Honors:
Bioengineering
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Siyang Zheng, Thesis Supervisor
  • William O Hancock, Honors Advisor
  • Peter J Butler, Faculty Reader
Keywords:
  • Cancer
  • CTC
  • Isolation
  • Characterization
  • Tumor
  • Membrane
  • Mechanics
  • Cell
  • Expansion
  • Osmosis
  • Microfluidics
  • Viscoelasticity
Abstract:
The study of circulating tumor cells (CTCs) has been at the forefront of cancer research in recent years. CTC isolation and characterization can yield significant insight into the type of tumor in question and its progression with treatment. A primary method of CTC isolation relies on their distinctive mechanical properties compared to other blood cells. Namely, CTCs have been found to be larger and more deformable than white blood cells, their closest counterparts in blood. However, no holistic mechanical model describing these behaviors exists. In order to better design CTC isolation technologies, the dynamics of different cell types as they expanded were studied and compared. Cancer cells were found to expand significantly, much more than the elasticity of the cell membrane would normally allow. We hypothesize that this is due to the presence of membrane folds that flatten out as the cell expands. We used microfluidics and hypotonic pressure to expand the cells and MATLAB image processing to analyze the response. Finally, we mapped the results to the equivalent dynamic behavior of a Kelvin-Voight viscoelastic material. We also modeled the osmotic pressure gradient influence on expansion over time. Our findings support the feasibility of using mechanical differences to improve CTC isolation and characterization in microfluidic devices. Cancer cells were significantly larger and more deformable than peripheral blood mononuclear cells. Moreover, it was found that different cancer cells exhibit unique expansion dynamics, suggesting a possible avenue for phenotyping unknown tumor cells.