Transforming growth factor dependent changes in healthy and tumor cells in a microfluidic environment*

Cellular response to change in transforming growth factor (TGF) in the extracellular domain is necessary for the growth of healthy cells and prevention of benign tumors from progressing to malignancy. However, the change in reaction kinetics on cell surface with extracellular transport is still poorly understood. We investigated the tumor microenvironment with a hybrid PDE-ODE based model in which advection, diffusion and reaction in the extracellular environment as well as protein/receptor interactions at cell surface are described using immersed interface method coupled with a system of ODEs. The extracellular flow conditions are resolved using an immersed boundary approach. The pathway-based ODE model requires quantification of a number of unknown parameters, such as kinetic rate constants and initial concentrations. These parameters are estimated using Bayesian inference with experimental data of TGF concentration on the cell surface for a wide range of experimental results on PE25 cell line. Our modeling results reveal that changes in the intercellular distance and flow conditions can alter the reaction dynamics appreciably.