Mathematical model of the multi-amino acid multi-transporter system in CHO cells

Mammalian cells express a large number of amino acid transporters of multiple types that can transfer multiple amino acids with varying efficacies. This combinatorial transfer makes it challenging to predict the effect of perturbations in the external amino acid pool or transporter expression levels on individual amino acid flux. Building on existing models, we develop a general model for such a complex transport system. Steady state analysis is carried out for single-carrier systems, and an analytical solution is derived for the transport rate under constant cellular and external concentrations. We apply the model to Chinese hamster ovary (CHO) cells in chemically defined media and estimate the short-term effects of perturbations in transporter expression and medium concentration on amino acid fluxes. Conditions for synergistic and repressive effects are identified, and the model can successfully predict known amino acid interactions and dependencies that were not used in constructing the model. This model can act as a tool to formulate testable hypotheses on the effect of process and genetic changes on amino acid initial uptake. Coupled with amino acid metabolism models, it can serve as the transporter dynamics component of a comprehensive model for intra- and extra-cellular amino acid dynamics.