Modeling of Multiple Steady States in Mammalian Cells. A Cybernetic Approach

Abstract

Mammalian cells utilize glucose and glutamine as the two key substrates. These two nutrients are complementary and substitutable in nature and, in cellular metabolism, can be oxidized completely, or be converted to excreted metabolites. The ability of cells to grow at the same rate at different physiological states gives rise to multiple steady states in continuous culture. Experimental results indicate that the steady state reached is strongly dependent on the initial condition of cultivation, or the reaction path. However, it has been elusive to develop a correlation between initial conditions and the resulting steady states. We have used a cybernetic model as the conceptual framework to explore the effect of initial conditions on the behavior of continuous cultures. The results of simulation demonstrate that a cybernetic model is capable of illustrating the effect of the history of a culture on the resulting steady state.