Transition Probability Cell Cycle Model. Part II—Nonbalanced Growth

A cell cycle model based on the transition probability model of Smith & Martin has been extended to non-balanced growth conditions in batch cultures. The model considers transition to a quiescent cell fraction, variable maturity-velocity, exogenous maintenance, and cell death. This extended model is capable of describing a large range of cell culture behavior which may not conform to Monod kinetics. The use of a constant quiescent transition allows the population to enter a stationary phase, but with a very large A-state to B-phase cell ratio. A substrate dependent quiescent transition helps to reduce this ratio while maintaining the general features of the population growth curves. A model with substrate dependent variable maturity-velocity qualitatively is similar to the Monod equation, while providing additional information on population distribution. The combination of quiescent transition and a substrate dependent maturity-velocity is also examined, and the resulting model is shown to capture the essence of both features.