Coupling between feedback loops in autoregulatory networks affects bistability range, open-loop gain and switching times.
Coupling between feedback loops in autoregulatory networks affects bistability range, open-loop gain and switching times.
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DOI：
10.1088/1478-3975/9/5/055003
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发表时间：
2012-10
期刊：
影响因子：
2
通讯作者：
Igoshin OA
中科院分区：
文献类型：
--
作者：
Tiwari A;Igoshin OA
控制应激反应、分化和细胞周期等多种细胞过程的生化调节网络通常包含耦合的反馈回路。我们的目标是了解反馈架构的特征（例如循环数量、循环符号及其耦合类型）如何影响网络动态性能。具体来说，我们研究了具有转录正反馈的网络的双稳定性范围、最大开环增益和切换时间如何受到与另一个正反馈环或负反馈环的加法或乘法耦合的影响。我们表明，网络的双稳态范围与其最大开环增益正相关，并且这两个量都取决于反馈环路的符号和反馈耦合的类型。此外，我们发现，如果我们控制两个系统信号响应曲线中的基础水平，添加正反馈可能会降低双稳态范围。此外，如果负反馈的解离常数远低于正反馈的解离常数，则添加负反馈可以增加双稳态范围。我们还发现，向双稳态网络添加正反馈会增加其双稳态范围的稳健性，而添加负反馈则会降低其双稳态范围的稳健性。最后，我们表明从高稳态过渡到低稳态的转换时间随着基因调控的有效倍数变化而增加。总之，我们表明耦合反馈环路对双稳范围和开关时间的影响取决于潜在的机制细节。
Biochemical regulatory networks governing diverse cellular processes such as stress-response, differentiation and cell cycle often contain coupled feedback loops. We aim to understand how features of feedback architecture, such as the number of loops, the sign of the loops and the type of their coupling, affect network dynamical performance. Specifically, we investigate how bistability range, maximum open-loop gain and switching times of a network with transcriptional positive feedback are affected by additive or multiplicative coupling with another positive or negative feedback loop. We show that a network’s bistability range is positively correlated with its maximum open-loop gain and that both the quantities depend on the sign of the feedback loops and the type of feedback coupling. Moreover, we find that the addition of positive feedback could decrease the bistability range if we control the basal level in the signal-response curves of the two systems. Furthermore, the addition of negative feedback has the capacity to increase the bistability range if its dissociation constant is much lower than that of the positive feedback. We also find that addition of a positive feedback to a bistable network increases robustness of its bistability range, whereas addition of a negative feedback decreases it. Finally, we show that the switching time for a transition from a high to a low steady state increases with the effective fold change in gene regulation. In summary, we show that the effect of coupled feedback loops on the bistability range and switching times depends on the underlying mechanistic details.
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影响因子：
64.8
作者：
Becskei, A;Serrano, L
通讯作者：
Serrano, L
影响因子：
64.8
作者：
Austin, DW;Allen, MS;Simpson, ML
通讯作者：
Simpson, ML
影响因子：
2
作者：
Pfeuty, Benjamin;Kaneko, Kunihiko
通讯作者：
Kaneko, Kunihiko
DOI：
10.1126/science.1160617
发表时间：
2008-10-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Brandman O;Meyer T
通讯作者：
Meyer T
影响因子：
3.6
作者：
Igoshin, Oleg A.;Alves, Rui;Savageau, Michael A.
通讯作者：
Savageau, Michael A.