The integration of self-reproduction, cell cycle and cell load—analysis of growth space and boundaries

Abstract One of the most significant achievements in describing and understanding the cell cycle in bacteria was the development of the Cooper-Helmstetter-Donachie theory. But this theory and very successful constraint-based metabolic network models have existed in parallel: the former does not quantitatively consider metabolic fluxes, and the latter analyse self-reproducing biomass instead of cells. Recently, we presented a theoretical analysis of the self-reproduction and growth of unit cells (UCs). In this paper, the analysis is expanded to the complete growth ranges of cells by merging the description of the self-reproduction system of the cell, the UC and Cooper-Helmstetter-Donachie cell cycle theory on a single-cell level. This allows a comprehensive, quantitatively relevant bottom-up approach to be applied to the analysis of bacterial cells growing in steady state. The integrated model enables the estimation of theoretical growth boundaries, respective limiting factors, and we show that the fastest growth is associated with medium-sized cells.