Noise-induced Min phenotypes in E. coli.
Noise-induced Min phenotypes in E. coli.
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DOI：
10.1371/journal.pcbi.0020080
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发表时间：
2006-06-30
影响因子：
4.3
通讯作者：
Elf J
中科院分区：
文献类型：
--
作者：
Fange D;Elf J
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。之前已经提出了 Min 系统的几种定量模型，但没有一个模型能够解释所有记录的突变表型的行为。我们分析了几种大肠杆菌突变体的 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 −）细胞可以通过平均场模型很好地表征，但需要随机模型来解释球形（rodA−）和磷脂酰乙醇酰胺缺陷（PE−）表型的几个特征。对于球形电池，平均场模型是双稳态的，系统可能陷入非振荡状态。然而，当考虑固有噪声时，仅保留实验观察到的振荡行为。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 区域沿内膜的偶尔滑动。对于 PE− 突变体，随机模型将随机局部且密集的 MinD 簇的出现解释为成核现象，其中低拷贝数的随机动力学导致高 MinDATP 到 MinDADP 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 系统的简单五反应模型可以解释所有记录的 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会导致表型差异。活细胞内的许多分子在反应之间没有时间扩散到整个细胞。此外，化学反应是随机且离散的事件。在这项研究中，作者研究了一个例子，当我们试图了解生物系统如何工作时，需要考虑细胞内化学的这些方面。作者研究了大肠杆菌 Min 系统显示的空间振荡模式。在野生型大肠杆菌中，Min 蛋白在细胞极之间来回振荡，以帮助细菌在细胞分裂前找到其中间位置。作者使用计算机模拟来解释为什么振荡模式会改变它们在大肠杆菌不同突变体中的表现方式。他们发现，只有考虑化学反应的随机性和离散性以及过程的空间特征，才能解释其中两种突变表型。特别有趣的是磷脂酰乙醇酰胺缺陷表型，其中大而密集的 MinD 蛋白簇在膜上的随机位置出现一段时间。作者认为，这种表型是由于成核现象造成的，其中低拷贝数的随机动力学被放大到宏观比例。
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.
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影响因子：
56.9
作者：
Coggan, JS;Bartol, TM;Sejnowski, TJ
通讯作者：
Sejnowski, TJ
影响因子：
2.3
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