Chen Meng, Wang Liming, Liu Chang C, Nie Qing
Department of Mathematics and §Department of Biomedical Engineering, University of California at Irvine , Irvine, California 92697, United States.
ACS Synth Biol. 2013 Oct 18;2(10):587-93. doi: 10.1021/sb400044g. Epub 2013 Jun 25.
Biological switches must sense changes in signal concentration and at the same time buffer against signal noise. While many studies have focused on the response of switching systems to noise in the ON state, how systems buffer noise at both ON and OFF states is poorly understood. Through analytical and computational approaches, we find that switching systems require different dynamics at the OFF state than at the ON state in order to have good noise buffering capability. Specifically, we introduce a quantity called the input-associated Signed Activation Time (iSAT) that concisely captures an intrinsic temporal property at either the ON or OFF state. We discover a trade-off between achieving good noise buffering in the ON versus the OFF states: a large iSAT corresponds to noise amplification in the OFF state in contrast to noise buffering in the ON state. To search for biological circuits that can buffer noise in both ON and OFF states, we systematically analyze all three-node circuits and identify mutual activation as a central motif. We also study connections among signal sensitivity, iSAT, and noise amplification. We find that a large iSAT at the ON state maintains signaling sensitivity while minimizing noise propagation. Taken together, the analysis of iSATs helps reveal the noise properties of biological networks and should aid in the design of robust switches that can both repress noise at the OFF state and maintain a reliable ON state.
生物开关必须感知信号浓度的变化，同时抵御信号噪声。虽然许多研究聚焦于开关系统在开启状态下对噪声的响应，但对于系统在开启和关闭状态下如何缓冲噪声却知之甚少。通过分析和计算方法，我们发现开关系统在关闭状态下需要与开启状态不同的动力学，以便具备良好的噪声缓冲能力。具体而言，我们引入了一个名为输入相关带符号激活时间（iSAT）的量，它简洁地捕捉了开启或关闭状态下的一种内在时间特性。我们发现在开启状态与关闭状态下实现良好噪声缓冲之间存在一种权衡：与开启状态下的噪声缓冲相反，大的iSAT对应着关闭状态下的噪声放大。为了寻找能在开启和关闭状态下都缓冲噪声的生物电路，我们系统地分析了所有三节点电路，并确定相互激活是一个核心基序。我们还研究了信号敏感性、iSAT和噪声放大之间的联系。我们发现开启状态下大的iSAT能保持信号敏感性，同时使噪声传播最小化。综合来看，对iSAT的分析有助于揭示生物网络的噪声特性，应该有助于设计出既能在关闭状态下抑制噪声又能维持可靠开启状态的稳健开关。
