Abstract
AbstractPopulation heterogeneity is due to intrinsic and extrinsic noises; cell to cell variability is related to cell partitioning at division and external forcing by the environment. In this article, a Monte‐Carlo calculation of integral source terms is coupled to a compartment approach. The biological phase is represented by an ensemble of discrete particles which are equipped with a coarse‐grained model that describes the intracellular response to extracellular conditions. The redistribution of cell properties at division generates unbalanced cells and introduces additional time scales into the population dynamics. Using this fully two‐way coupled approach, the consequences of repeated exposure to feast and famine events on both the reactor and the population heterogenities are investigated in a CSTR+PFR scale‐down bioreactor. It is shown that the integration of intrinsic noise due to cell division continuously produces cells that are not at equilibrium with their environment and this contributes to population heterogeneity, even in homogeneous environments.
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