Noise-Induced Min Phenotypes in E. coli

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Abstract
The spatiotemporal oscillations of the Escherichia coli proteins MinD and MinE direct cell division to the region between the chromosomes. Several quantitative models of the Min system have been suggested before, but no one of them accounts for the behavior of all documented mutant phenotypes. We analyzed the stochastic reaction-diffusion kinetics of the Min proteins for several E. coli mutants and compared the results to the corresponding deterministic mean-field description. We found that wild-type (wt) and filamentous (ftsZ −) cells are well characterized by the mean-field model, but that a stochastic model is necessary to account for several of the characteristics of the spherical (rodA−) and phospathedylethanolamide-deficient (PE−) phenotypes. For spherical cells, the mean-field model is bistable, and the system can get trapped in a non-oscillatory state. However, when the intrinsic noise is considered, only the experimentally observed oscillatory behavior remains. The stochastic model also reproduces the change in oscillation directions observed in the spherical phenotype and the occasional gliding of the MinD region along the inner membrane. For the PE− mutant, the stochastic model explains the appearance of randomly localized and dense MinD clusters as a nucleation phenomenon, in which the stochastic kinetics at low copy number causes local discharges of the high MinDATP to MinDADP potential. We find that a simple five-reaction model of the Min system can explain all documented Min phenotypes, if stochastic kinetics and three-dimensional diffusion are accounted for. Our results emphasize that local copy number fluctuation may result in phenotypic differences although the total number of molecules of the relevant species is high. Many molecules inside a living cell do not have time to diffuse through the whole cell in-between reactions. Furthermore, the chemical reactions are random and discrete events. In this study, the authors study an example in which these aspects of intracellular chemistry need to be considered when we try to understand how a biological system works. The authors have investigated the spatial oscillation patterns that are displayed by the Min system of Escherichia coli. In wild-type E. coli, the Min proteins oscillate back and forth between the cell poles to help the bacterium find its middle before cell division. The authors used computer simulations to explain why the oscillation patterns change the way they do in different mutants of E. coli. They find that two of the mutant phenotypes can only be explained if one considers the randomness and discreteness of chemical reactions in addition to the spatial characteristics of the process. Particularly interesting is the phospathedylethanolamide-deficient phenotype, in which large dense clusters of MinD protein appear for some time at random locations on the membrane. The authors believe that this phenotype is due to a nucleation phenomenon, in which the stochastic kinetics at low copy number is amplified to macroscopic proportions.