A Monte Carlo simulation of the Escherichia coli cell cycle

Abstract

A Monte-Carlo simulation of the division cycle of an individual bacterium has been developed to test theories concerning the control of cell cycle events and for the analysis of cell cycle data. The model is based on the work of Cooper and Helmstetter and other theories concerning the control of DNA replication initiation, chromosome segregation and cell division. Variability in the molecular events that initiate a particular cell cycle event is incorporated using a Monte Carlo approach. The model results are compared with experimental data from a number of different sources and collected using a number of different analytical techniques. This model is able to accurately represent the cell size distributions of an exponentially growing population as determined by a Coulter Counter and the DNA distributions as determined by flow cytometry. The model is also able to accurately simulate the cell age distribution and chromosome replication and segregation patterns as determined by the membrane-elution technique. Results from parameter sensitivity analysis indicate that variability in the symmetry of cell division and in the cell size at initiation of chromosome replication have the most significant impact on the cell size, age and DNA distributions. Results from the membrane-elution simulation support the hypothesis that total cell protein is synthesized exponentially during the division cycle and that cell size control is a plausible explanation for control of DNA replication. The simulation results for chromosome segregation agree with experimental data and support chromosome strand segregation models. In the future, this simulation should be useful in testing complex theories about molecular control of cell cycle events against experimental data.