Fange David, Elf Johan
Department of Cell and Molecular Biology, Biomedical Centre, Uppsala University, Uppsala, Sweden.
PLoS Comput Biol. 2006 Jun 30;2(6):e80. doi: 10.1371/journal.pcbi.0020080. Epub 2006 May 18.
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 MinD(ATP) to MinD(ADP) 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.
大肠杆菌蛋白MinD和MinE的时空振荡将细胞分裂引导至染色体之间的区域。此前已提出了几种Min系统的定量模型,但没有一个能解释所有已记录的突变体表型的行为。我们分析了几种大肠杆菌突变体中Min蛋白的随机反应扩散动力学,并将结果与相应的确定性平均场描述进行了比较。我们发现野生型(wt)和丝状(ftsZ-)细胞可以用平均场模型很好地描述,但需要一个随机模型来解释球形(rodA-)和磷脂酰乙醇胺缺陷型(PE-)表型的几个特征。对于球形细胞,平均场模型是双稳态的,系统可能会陷入非振荡状态。然而,当考虑内在噪声时,只有实验观察到的振荡行为仍然存在。随机模型还再现了在球形表型中观察到的振荡方向的变化以及MinD区域偶尔沿内膜的滑动。对于PE-突变体,随机模型将随机定位且密集的MinD簇的出现解释为一种成核现象,其中低拷贝数下的随机动力学导致高MinD(ATP)到MinD(ADP)电位的局部放电。我们发现,如果考虑随机动力学和三维扩散,Min系统的一个简单的五反应模型可以解释所有已记录的Min表型。我们的结果强调,尽管相关物种的分子总数很高,但局部拷贝数波动可能导致表型差异。