Antithetic Integral Feedback Ensures Robust Perfect Adaptation in Noisy Biomolecular Networks
Antithetic Integral Feedback Ensures Robust Perfect Adaptation in Noisy Biomolecular Networks
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DOI：
10.1016/j.cels.2016.01.004
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发表时间：
2016-01-27
期刊：
影响因子：
9.3
通讯作者：
Khammash, Mustafa
中科院分区：
文献类型：
--
作者：
Briat, Corentin;Gupta, Ankit;Khammash, Mustafa
适应刺激的能力是许多生物系统的定义特征，对维持体内平衡至关重要。虽然人们很好地理解，当网络表现出确定性时，负反馈可以用来实现稳态，但噪声对其调节功能的影响尚不清楚。在这里，我们结合联合收割机的概率和控制理论，开发一个生物调节的理论，明确考虑到生物化学反应的噪声性质。我们介绍了用于分析和设计鲁棒稳态电路的工具，并提出了一种新的调节基序，我们称之为对立积分反馈。这个基序利用随机噪声，使其能够在类似的确定性调节失败的情况下实现精确调节。具体来说，对偶积分反馈保持了整个网络的稳定性，将任何受调节物种的种群引导到所需的设定点，并完美地适应。我们认为，这个主题可能是普遍存在于内源性生物电路和有用的合成电路时，创建。
The ability to adapt to stimuli is a defining feature of many biological systems and critical to maintaining homeostasis. While it is well appreciated that negative feedback can be used to achieve homeostasis when networks behave deterministically, the effect of noise on their regulatory function is not understood. Here, we combine probability and control theory to develop a theory of biological regulation that explicitly takes into account the noisy nature of biochemical reactions. We introduce tools for the analysis and design of robust homeostatic circuits and propose a new regulation motif, which we call antithetic integral feedback. This motif exploits stochastic noise, allowing it to achieve precise regulation in scenarios where similar deterministic regulation fails. Specifically, antithetic integral feedback preserves the stability of the overall network, steers the population of any regulated species to a desired set point, and adapts perfectly. We suggest that this motif may be prevalent in endogenous biological circuits and useful when creating synthetic circuits.