Date of Award
Master of Science
Tumor repopulating cells (TRC) from melanoma tumors can invade into distant healthy tissues and generate secondary tumors. The mechanical properties of TRCs are very distinct from non-TRC populations. They are very soft compared to non-TRCs and can sustain in very soft micro-environments. Our own preliminary data on TRCs revealed that they exhibit an unusual behavior of restricted spreading and generate very few focal adhesions. In contrast to TRCs, non-TRCs spread more in response to mechanical cues. By utilizing the shape factor of non-spreading TRCs to rapidly isolate them by a gentle shear flow we developed a 3-D FEM model to address the problem in a more systematic way. We identified an optimum micro-shear flow through a 1000x100 micrometer2 cross-sectional channel to isolate TRCs. We used customized ANSYS Fluent and Static Structural analysis termed as 1-way FSI, where generated result for micro-shear fluid flow in Fluent was imported to static structural analysis to find the impact on overall cells. Mechanical properties of focal adhesion remain almost similar in both TRCs and non-TRCs, but number of focal adhesion varies significantly between these two groups- which was used in designing and setting the mechanical properties of focal adhesions of all the cells in ANSYS Design Modeler and Engineering properties respectively. Additional calculation was done to find out how much flow rate should be generated to remove the non-TRCs of various geometrical shape. After analyzing all the data, the optimum micro-shear flow was found out to be 0.3384 m/s or 33.84 µl/s to isolate the TRCs only, but the non-TRCs. Our extended analysis also showed the flow rate required to dislodge non-TRCs as well. Many have reported that use of biomarkers to identify TRCs have been inefficient. But utilizing our method in physical experiment will ensure to dislodge TRCs from matrix. Then further investigation can be conducted to characterize TRCs which will eventually help to control metastasis.
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