Modeling the Cell Cycle Response to Carbon and Nitrogen deprivation in Caulobacter Populations

Abstract

AbstractCaulobacter crescentus inhabits a wide range of aquatic ecosystems, including environments with poor nutrients. It undergoes an asymmetrical cell division cycle, generating a pair of daughter cells with distinct motility and replicative potentials. Caulobacter populations have the flexibility to save energy by halting chromosome replication and reduce intraspecific competition by settling in different places in environments. The control mechanisms underlying Caulobacter cell development have been well studied under nutrient-rich conditions, however, its mechanism of response to stressful changes is not fully understood. Here we present a mathematical model to analyze the starvation responses in Caulobacter. We investigate several known starvation signaling pathways to study how these pathways influence cell cycle development and explain experimental observations of starved Caulobacter populations. We also apply a new parameterization strategy to mathematical modeling of biological systems, whose diverse communities have to be robust with many parameter variations, while still having accurate control to maintain regular cell cycle dynamics. Our model demonstrates that the guanine-based second messenger, c-di-GMP (cdG), plays important roles to immediately arrest the cell cycle of Caulobacter under nutrient deprivation; however, it is not sufficient to cause the robust arrest. Our model suggests there should be unknown pathway(s) reducing the levels of CtrA under starvation condition, which results in a significant delay in cytokinesis of starved stalked Caulobacter cells.