Bioengineering Technical Component 6.1 Rationale for the Use of Bioengineered Devices Two of the greatest challenges in developing a modern, quantitative, mathematical model of cancer invasion are to determine the values of the parameters required to specify the model, and to validate through experiments the predictions of the model. This is complicated by the multiscale nature of the model: cellular, subcellular, and molecular. Thcrc arc a large number of biochemical and molecular biological techniques to study cancer at the molecular level. However, the model we propose will be, at least initially, focused largely on the cellular and subeellular level, and will predict cellular parameters such as cell detachment, migration, metabolic activity, proliferation, death, and mutation, and microenviromental parameters such ECM degradation? angiogenesis, and inflammation. While fluorescence imaging is an excellent method to visualize cells and organelles, and even molecular binding, there is a paucity of techniques to fluantify the mechanical and metabolic behavior of cancer cells. Technical obstacles include the difficulties in measuring cellular metabolic activity, in generating stable and controllable gradients, measuring cellular forces directly, and assessing motility in a multieellular environment in real time. For example, NIVIR spectroscopy has been used to determine the metabolic enviromment, e.g., pH, within a tumor [92,210-212], but the spatial resolution that can be achieved with this approach is not consistent with small-scale laboratory cultures ef cancer cells [213] or even the heterogeneity observed within tumors in vivo. Furthermore, it is necessary to measure multiple metabolic parameters such as pH, oxygen, gtucese, and lactate to specify a metabolic activiV based upon a realistic model of celluar metabolism.
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