Mathematical Model for Tissue-Level Hypoxic Response in Microfluidic Environment

Abstract

Availability of essential species like oxygen is critical in shaping the dynamics of tumor growth. When the intracellular oxygen level falls below normal, it initiates major cascades in cellular dynamics leading to tumor cell survival. In a cellular block with cells growing away from the blood vessel, the scenario can be aggravated for the cells further inside the block. In this study, the dynamics of intracellular species inside a colony of tumor cells are investigated by varying the cell-block thickness and cell types in a microfluidic cell culture device. The oxygen transport across the cell block is modeled through diffusion, while ascorbate (AS) transport from the extracellular medium is addressed by a concentration-dependent uptake model. The extracellular and intracellular descriptions were coupled through the consumption and traffic of species from the microchannel to the cell block. Our model shows that the onset of hypoxia is possible in HeLa cell within minutes depending on the cell location, although the nutrient supply inside the channel is maintained in normoxic levels. This eventually leads to total oxygen deprivation inside the cell block in the extreme case, representing the development of a necrotic core that maintains a dynamic balance with growing cells and scarce supply. The numerical model reveals that species concentration and hypoxic response are different for HeLa and HelaS3 cells. Results also indicate that the long-term hypoxic response from a microfluidic cellular block stays within 5% of the values of a tissue with the basal layer. The hybrid model can be very useful in designing microfluidic experiments to satisfactorily predict the tissue-level response in cancer research.