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Application of hybrid cybernetic model in simulating myeloma cell culture co-consuming glucose and glutamine with mixed consumption patterns

Paper ID Volume ID Publish Year Pages File Format Full-Text
34749 45042 2013 10 PDF Available
Title
Application of hybrid cybernetic model in simulating myeloma cell culture co-consuming glucose and glutamine with mixed consumption patterns
Abstract

•First time application of hybrid cybernetic model in mammalian cell culture.•Demonstrate the scalability and availability of HCM in more complex system.•Perfect simulation of mammalian cell culture.•Precise prediction of mammalian cell culture.

A dynamic model called hybrid cybernetic model (HCM) based on structured metabolic network is established for simulating mammalian cell metabolism featured with partially substitutable and partially complementary consumption patterns of two substrates, glucose and glutamine. Benefiting from the application of elementary mode analysis (EMA), the complicated metabolic network is decomposed into elementary modes (EMs) facilitating the employment of the hybrid cybernetic framework to investigate the external and internal flux distribution and the regulation mechanism among them. According to different substrate combination, two groups of EMs are obtained, i.e., EMs associated with glucose uptake and simultaneous uptake of glucose and glutamine. Uptake fluxes through various EMs are coupled together via cybernetic variables to maximize substrate uptake. External fluxes and internal fluxes could be calculated and estimated respectively, by the combination of the stoichiometrics of metabolic networks and fluxes through regulated EMs. The model performance is well validated via three sets of experimental data. Through parameter identification of limited number of experimental data, other external metabolites are precisely predicted. The obtained kinetic parameters of three experimental cultures have similar values, which indicates the robustness of the model. Furthermore, the prediction performance of the model is successfully validated based on identified parameters.

Keywords
Hybrid cybernetic model (HCM); Elementary modes (EMs); Mammalian cell culture; Metabolic network; Model validation
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Application of hybrid cybernetic model in simulating myeloma cell culture co-consuming glucose and glutamine with mixed consumption patterns
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Publisher
Database: Elsevier - ScienceDirect
Journal: Process Biochemistry - Volume 48, Issues 5–6, May–June 2013, Pages 955–964
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us