Cybernetic modeling and regulation of metabolic pathways in multiple steady states of hybridoma cells

Hybridoma cells utilize a pair of complementary and partially substitutable substrates, glucose and glutamine, for growth. It has been shown that cell ular metabolism shifts under different culture conditions. When those cultu res at different metabolic states are switched to a continuous mode, they r each different steady states under the same operating conditions. A cyberne tic model was constructed to describe the complementary and partial substit utable nature of substrate utilization. The model successfully predicted th e metabolic shift. and multiple steady-state behavior. The results are cons istent with the experimental observation that the history of the culture af fects the resulting steady state.