Modeling heterogeneity in a cell culture using a coupled population balance-oxidative stress model

Abstract

Population balance models (PBMs) were formulated to describe the evolution in time of the cell population in terms of growth and oxidative stress. Flow cytometry data was used to gain insight into the distribution of important quantities (e.g., cell size, intracellular concentrations of metabolites) over the entire cell population. A coupled population balance-oxidative stress model was developed to predict distributions in cell size and intracellular glutamate, ROS, NADPH and NADP+ concentrations in shake flask cultures of B. pertussis. The major advantage of using a PBM is that it accounts for the distributions and can predict the heterogeneity of the cell population with respect to experimental conditions that are averaged out in bulk models. When comparing the coupled population balance – oxidative stress model to the bulk oxidative stress model, it is apparent that the PBM provides much better predictions of the intracellular ROS concentration. We hypothesize that due to the nonlinear relations between cell growth and oxidative stress, intracellular and cell surface quantities can be better modeled with population balance models.