Fluctuations and quality of control in biological cells: Zero-order ultrasensitivity reinvestigated
Fluctuations and quality of control in biological cells: Zero-order ultrasensitivity reinvestigated
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DOI：
10.1016/s0006-3495(00)76377-6
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发表时间：
2000-09-01
影响因子：
3.4
通讯作者：
Ehrenberg, M
中科院分区：
文献类型：
--
作者：
Berg, OG;Paulsson, J;Ehrenberg, M
活细胞与大多数其他化学系统的不同之处在于，它们涉及非常非线性地依赖于每个细胞低拷贝数的化学物质的调节途径。这导致了各种各样的细胞内动力学现象，这些现象逃避了宏观建模，宏观建模隐含地假设细胞是无限大的，波动可以忽略不计。在需要精确性和可靠性的情况下，第二章对评估波动如何影响监管特别重要。在这里，考虑到有限的细胞尺寸和随机方面，我们在理论上重新研究了用于靶酶的共价修饰的零级超灵敏度的机制（Goldbeter和Koshland（1981）Proc. Natl. Acad. Sci. USA. 78：6840-6844）。在宏观上，这种机制可以在转化酶活性的非常小的变化下产生目标浓度的非常急剧的转变。这项研究表明，在有限细胞或有限细胞的人口的过渡是渐进得多。它还表明，开关是完全类似的热力学相变，超灵敏度是不可避免地耦合到随机超变。因此，大量细胞的平均反应通常比宏观描述预测的要平缓得多。
Living cells differ from most other chemical systems in that they involve regulation pathways that depend very nonlinearly on chemical species that are present in low copy numbers per cell. This leads to a variety of intracellular kinetic phenomena that elude macroscopic modeling, which implicitly assumes that cells are infinitely large and fluctuations negligible. II is of particular importance to assess how fluctuations affect regulation in cases where precision and reliability are required. Here, taking finite cell size and stochastic aspects into account, we reinvestigate theoretically the mechanism of zero-order ultrasensitivity for covalent modification of target enzymes (Goldbeter and Koshland (1981) Proc. Natl. Acad. Sci. USA. 78:6840-6844). Macroscopically, this mechanism can produce a Very sharp transition in target concentrations for very small changes in the activity of the converter enzymes. This study shows that the transition is much more gradual in a finite cell or a population of finite cells. It also demonstrates that the switch is exactly analogous to a thermodynamic phase transition and that ultrasensitivity is inevitably coupled to random ultravariation. As a consequence, the average response in a large population of cells will often be much more gradual than predicted from macroscopic descriptions.