Mathematical Modeling of Iron Uptake by Tim‐2 Receptor in Mouse Kidney Cells

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Iron is an essential element in all living cells. Classically, cells acquire iron through transferrin‐transferrin receptor pathway. In addition to this pathway, iron can be taken up through H‐ferritin (HFt) binding to Tim‐2 receptor in mice. In this research, the iron uptake process through Tim‐2 was computed by mathematical models to illustrate the dynamics of iron uptake, storage, and export in mice kidney cells. Simulation results showing iron metabolic process by Tim‐2 pathway were compared with biological experimental data done in vitro. The model predicts the fates of HFt and iron in Tim‐2 pathway and produces equations to calculate rate of iron flow within different cellular compartments. The model predicts desirable characteristics for intracellular iron homeostasis and reveals that the rate of iron storage in endogenous intracellular ferritin is around 2.8% per minute, and export rate through non‐Tim2 protein is about 1.0% per minute. The model incorporates three iron metabolic experiments in different time scale under one consistent framework. The model captures the complexity of iron metabolism and connects several metabolic processes into one picture for easy understanding. The model can be applied to general iron metabolism in other cell types.