Application of population balance techniques to the modelling of the cell cycle

A generic, structural segregated model of the cellular life cycle has been developed. The basis of the model is segregation of the cell cycle in terms of biological age. The model employs a population balance approach and is solved using Euler integration. The main features of this generic model can be summarised as follows: (i) a flexible number of cell cycle phases, (ii) deterministic and stochastic control of phase durations, (iii) full interaction between all cell cycle phases, (iv) independent phase interaction with a pre-defined multicomponent media, (v) internal cellular pools which account for all media components and internal biochemical intermediates, (vi) interaction between all internal cellular pools which can be described using a number of standard chemical interactions. A number of the properties of this model have been investigated by simulating some complex propagation strategies: the periodic feeding of nutrients in chemostat cultures and the effect of cell resuspension and media dilution in batch fermentation. Some of the features unique to this type of model, such as partial synchronisation, are highlighted in this paper. Furthermore, the potential applications in fields ranging from cancer research to process engineering will be discussed.