Transition probability cell cycle model with product formation

Abstract

A cell cycle population model based on the transition probability model of Smith and Martin (1973) has been extended to include product synthesis and export. The model handles two probable mechanisms. In the direct production model, the product is the protein. In the transcription model, the product is the specific mRNA. The protein is synthesized by translation of the specific mRNA and subsequently exported. In either case, the cell density is jointly distributed in the primary product and maturity age in the cell cycle. This extended model also is capable of describing a large range of conditions, including substrate dependent batch and continuous cultures. With the use of unity maturity‐velocity (but the transition rate a function of limiting substrate), the model is shown to exhibit a negative growth association between the specific productivity of monoclonal antibodies from hybridomas and the dilution rates of a chemostat. Possibilities of maturity age dependent transcription and translation are considered, and the results show that these features can amplify the specific productivity negative association with specific growth rate. While this model may provide a partial elucidation of monoclonal antibody productivity in a chemostat, the present work provides a proper framework with which probable cell cycle dependent product formation can be analyzed rigorously with a comprehensive computational model. © 1998 John Wiley & Sons, Inc. Biotechnol Bioeng 58:387–399, 1998.

Cyclin and DNA Distributed Cell Cycle Model for GS-NS0 Cells

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Effects of Three-Dimensional Culturing in a Fibrous Matrix on Cell Cycle, Apoptosis, and MAb Production by Hybridoma Cells

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Quantitative Analysis of Bacterial Gene Expression by Using the gusA Reporter Gene System

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