Morchain Jérôme, Quedeville Vincent, Fox Rodney O, Villedieu Philippe
TBI, CNRS, INRA, INSA, Université de Toulouse, Toulouse, France.
FERMaT, CNRS, INPT, INSA, UPS, Université de Toulouse, Toulouse, France.
Biotechnol Bioeng. 2021 Jul;118(7):2435-2447. doi: 10.1002/bit.27752. Epub 2021 May 10.
An original dynamic model for substrate uptake under transient conditions is established and used to simulate a variety of biological responses to external perturbations. The actual uptake and growth rates, treated as cell properties, are part of the model variables as well as the substrate concentration at the cell-liquid interface. Several regulatory loops inspired by the structure of the glycolytic chain are considered to establish a set of ordinary differential equations. The uptake rate evolves so as to reach an equilibrium between the cell demand and the environmental supply. This model does not contain any of the usual algebraic closure laws relating to the instantaneous uptake, growth rates, and the substrate concentration, nor does it enforce the continuity of mass fluxes at the liquid-cell interface. However, these relationships are found in the steady-state solution. Previously unexplained experimental observations are well reproduced by this model. Also, the model structure is suitable for further coupling with flux-based metabolic models and fluid-flow equations.
建立了一个用于瞬态条件下底物摄取的原始动态模型，并用于模拟对外部扰动的各种生物反应。作为细胞特性的实际摄取和生长速率，以及细胞 - 液体界面处的底物浓度，都是模型变量的一部分。受糖酵解链结构启发的几个调节回路被考虑用于建立一组常微分方程。摄取速率不断演变，以在细胞需求和环境供应之间达到平衡。该模型不包含任何与瞬时摄取、生长速率和底物浓度相关的常见代数封闭定律，也不强制在液 - 细胞界面处的质量通量连续性。然而，这些关系在稳态解中可以找到。该模型很好地再现了以前无法解释的实验观察结果。此外，该模型结构适合与基于通量的代谢模型和流体流动方程进一步耦合。
