Quantitative Modeling of the Molecular Mechanism Controlling the Asymmetric Cell Division Cycle in Caulobacter crescentus

Caulobacter crescentus is an important model organism for studying regulation of cell growth, division and differentiation in prokaryotes. C. crescentus undergoes asymmetric division producing two progeny cells with identical genome but different developmental programs: the "swarmer" cell is flagellated and motile, and the "stalked" cell is sessile (attached to a surface by its stalk and holdfast). Only stalked cells undergo chromosome replication and cell division. A swarmer cell must shed its flagellum and grow a stalk before it can enter the replication-division cycle. Based on published experimental evidence, we propose a molecular mechanism controlling the cell division cycle in this bacterium. Our quantitative model of the mechanism illustrates detailed temporal dynamics of regulatory proteins and corresponding physiological changes during the process of cell cycle progression and differentiation of wild-type cells (both stalked cells and swarmer cells) and of a number of known and novel mutant strains. Our model presents a unified view of temporal regulation of protein activities during the asymmetric cell division cycle of C. crescentus and provides an opportunity to study and analyze the system dynamics of the Caulobacter cell cycle (as opposed to the dynamics of individual steps). The model can serve as a starting point for investigating molecular regulations of cell division and differentiation in other genera of alpha-proteobacteria, such as Brucella and Rhizobium, because recent experimental data suggest that these alpha-proteobacteria share similar genetic mechanisms for cell cycle control.