Multiscale Modeling of Biopolymer Production in Multicellular Systems

In this contribution we present a multiscale modeling approach to systematically explore the heterogeneity of biopolymer production in multicellular systems. The first step is a dynamic single cell model which is based on the hybrid cybernetic modeling approach to include cell internal regulation. The single cell model is used for nonlinear analysis and the occurrence of multiple steady states is discussed. The single cell model is then reduced by using the lumped hybrid cybernetic approach and by approximation of enzyme levels. The reduced single cell model is used to develop a population balance model for predicting heterogeneity in multicellular production processes. Thus, we have combined the cybernetic modeling approach with population balance modeling, which consequently includes cell internal regulation. The multiscale modeling approach is first developed for the microorganism Ralstonia eutropha, which serves as a model and benchmark organisms. Good agreement between model predictions and experimental data is shown. An extension to Rhodospirillum rubrum is discussed, which shows interesting transient bimodal dynamics.