title: Analysis of Chinese hamster ovary cell metabolism through a combined computational and experimental approach.
abstract: Optimization of cell culture processes can benefit from the systematic analysis of experimental data and their organization in mathematical models, which can be used to decipher the effect of individual process variables on multiple outputs of interest. Towards this goal, a kinetic model of cytosolic glucose metabolism coupled with a population-level model of Chinese hamster ovary cells was used to analyse metabolic behavior under batch and fed-batch cell culture conditions. The model was parameterized using experimental data for cell growth dynamics, extracellular and intracellular metabolite profiles. The results highlight significant differences between the two culture conditions in terms of metabolic efficiency and motivate the exploration of lactate as a secondary carbon source. Finally, the application of global sensitivity analysis to the model parameters highlights the need for additional experimental information on cell cycle distribution to complement metabolomic analyses with a view to parameterize kinetic models.
authors.affiliation: Centre for Process Systems Engineering, Department of Chemical Engineering and Chemical Technology, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
authors.forename: Ning
authors.initials: N
authors.lastname: Chen
authors.forename: Mark H
authors.initials: MH
authors.lastname: Bennett
authors.forename: Cleo
authors.initials: C
authors.lastname: Kontoravdi