A Model of Aerobic and Anaerobic Metabolism in Cancer Cells – Parameter Estimation, Simulation, and Comparison with Experimental Results
DOI:
https://doi.org/10.3384/ecp21185465Keywords:
biological systems, cancer metabolism, simulation, parameter estimation, biotechnologyAbstract
We present a mathematical model of metabolism in cancer cells that is capable of describing both aerobic oxidative metabolism and anaerobic fermentation metabolism, and how cancer cells shift between these metabolic states when exposed to different substrates and different enzymatic inhibitors. The model is designed to be used in combination with experimental data gathered with an Agilent Seahorse XF metabolic analyzer. The model is parameterized in a manual tuning procedure to fit experimental data, and validated against experimental data from another setup, to which the model shows good conformity. We also investigate the structural identifiability of the model. The results indicate that the model is structurally identifiable, and that it can thus be uniquely parameterized, using the following 5 measurements: extracellular concentrations of glucose, glutamine and lactate, proton production rate (a Seahorse XF analyzer measurement) and oxygen consumption rate.References
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Copyright (c) 2022 Svein H. Stokka, Eivind S. Haus, Gunhild Fjeld, Tormod Drengstig, Kristian Thorsen
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