Emergence of qualitative states in synthetic circuits driven by ultrasensitive growth feedback.
Emergence of qualitative states in synthetic circuits driven by ultrasensitive growth feedback.
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DOI：
10.1371/journal.pcbi.1010518
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发表时间：
2022-09
影响因子：
4.3
通讯作者：
中科院分区：
文献类型：
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合成的基因电路与宿主生长之间的相互作用可能会导致电路的动力学行为出现意想不到的结果。然而，宿主细胞的生长是如何影响基因回路的稳定状态和稳定性的，目前还不完全清楚。在这里，我们根据已发表的实验数据，建立了一个非线性增长反馈的数学模型。模型分析预测，增长反馈可以显著改变系统的定性状态。在没有正反馈的电路中可能会出现双稳态，而在自激活和触发开关电路中会出现高阶多稳态(三个或更多稳态)。我们的结果为了解超灵敏生长反馈对合成电路中质态出现的潜在影响以及相应的潜在机制提供了洞察。合成基因回路与细胞生长之间的相互抑制作用在宿主回路系统中产生生长反馈。以往的研究表明，生长反馈可以显著影响宿主-电路系统的动力学。然而，增长反馈影响的复杂性还没有被完全理解。在这里，我们的数据分析显示了不同生长条件下细胞和合成基因回路之间超灵敏的生长反馈。为了研究超灵敏生长反馈对主电路系统的影响，我们建立了一个数学模型框架。我们的结果揭示了由超灵敏生长反馈引起的宿主-电路系统的定性态的出现。我们发现在一个带有构成启动子的简单的合成基因电路中出现了双稳现象。此外，在自激活和触发开关电路中也可以看到三稳定性。我们的研究揭示了超灵敏的生长反馈在合成基因回路和宿主相互作用中的作用。了解超灵敏生长反馈的效果可以帮助科学家和工程师识别基因电路中意想不到的结果，并制定控制策略。
The mutual interactions between the synthetic gene circuits and the host growth could cause unexpected outcomes in the dynamical behaviors of the circuits. However, how the steady states and the stabilities of the gene circuits are affected by host cell growth is not fully understood. Here, we developed a mathematical model for nonlinear growth feedback based on published experimental data. The model analysis predicts that growth feedback could significantly change the qualitative states of the system. Bistability could emerge in a circuit without positive feedback, and high-order multistability (three or more steady states) arises in the self-activation and toggle switch circuits. Our results provide insight into the potential effects of ultrasensitive growth feedback on the emergence of qualitative states in synthetic circuits and the corresponding underlying mechanism. The mutual inhibitory effect between synthetic gene circuits and cell growth produces growth feedback in the host-circuit system. Previous studies have demonstrated that the growth feedback could significantly impact the dynamics of the host-circuit system. However, the complexity of the growth feedback impact is not fully understood. Here, our data analysis displays ultrasensitive growth feedback between the cells and synthetic gene circuits under different growth conditions. To study the effect of ultrasensitive growth feedback on the host-circuit system, we develop a mathematical modeling framework. Our results reveal the emergence of qualitative states on the host-circuit system induced by ultrasensitive growth feedback. We found an emergence of bistability in a simple synthetic gene circuit with a constitutive promoter. Also, tristability could be seen in self-activation and toggle switch circuits. Our research uncovered the effect of ultrasensitive growth feedback in synthetic gene circuits and host interactions. Understanding the effects of ultrasensitive growth feedback could help scientists and engineers identify unexpected outcomes in gene circuits and formulate control strategies.
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影响因子：
3.4
作者：
Blanchard, Andrew E.;Liao, Chen;Lu, Ting
通讯作者：
Lu, Ting
影响因子：
64.8
作者：
Erickson DW;Schink SJ;Patsalo V;Williamson JR;Gerland U;Hwa T
通讯作者：
Hwa T
影响因子：
28.3
作者：
Liao, Chen;Blanchard, Andrew E.;Lu, Ting
通讯作者：
Lu, Ting
DOI：
10.1126/science.1240831
发表时间：
2013-08-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kueh HY;Champhekar A;Nutt SL;Elowitz MB;Rothenberg EV
通讯作者：
Rothenberg EV
影响因子：
9.9
作者：
Balakrishnan R;de Silva RT;Hwa T;Cremer J
通讯作者：
Cremer J