A hidden integral structure endows absolute concentration robust systems with resilience to dynamical concentration disturbances
A hidden integral structure endows absolute concentration robust systems with resilience to dynamical concentration disturbances
复制标题
DOI：
10.1098/rsif.2020.0437
复制
发表时间：
2020-10-28
影响因子：
3.9
通讯作者：
Khammash, Mustafa
中科院分区：
文献类型：
--
作者：
Cappelletti, Daniele;Gupta, Ankit;Khammash, Mustafa
在任何正的稳定状态下，在同一水平上表达某些感兴趣的化学物种的生化系统称为绝对浓度稳健(ACR)。这些物种的行为是稳定的、可预测的，在某种意义上，如果系统达到(可能是新的)正稳定状态，它们的表达对于物种浓度的突然变化是稳健的。这种特性已被证明在某些基因调控网络和信号系统中具有重要意义。在本文中，我们从数学上证明了Shina和Feinberg在2010年研究的一类著名的ACR系统隐藏了一个内部积分结构。这种结构赋予这些系统比以前所知的更高程度的稳健性。具体地说，可以抑制比物种浓度突然变化更普遍的干扰，并实现稳健的完美适应。值得注意的是，我们表明，当系统与其他化学反应网络互连时，这些性质保持不变。这一关键功能使绝缘体设备的设计能够缓冲来自下游系统的负载效应-这是合成生物学中模块化电路设计的关键要求。我们还注意到，当绝缘体的作用时间比上游模块(通常需要的)快时，绝缘体的最佳性能才能实现，但在我们的施工中，绝缘体的作用时间没有必要比下游模块快。
Biochemical systems that express certain chemical species of interest at the same level at any positive steady state are called 'absolute concentration robust' (ACR). These species behave in a stable, predictable way, in the sense that their expression is robust with respect to sudden changes in the species concentration, provided that the system reaches a (potentially new) positive steady state. Such a property has been proven to be of importance in certain gene regulatory networks and signaling systems. In the present paper, we mathematically prove that a well-known class of ACR systems studied by Shinar and Feinberg in 2010 hides an internal integral structure. This structure confers these systems with a higher degree of robustness than was previously known. In particular, disturbances much more general than sudden changes in the species concentrations can be rejected, and robust perfect adaptation is achieved. Significantly, we show that these properties are maintained when the system is interconnected with other chemical reaction networks. This key feature enables the design of insulator devices that are able to buffer the loading effect from downstream systems-a crucial requirement for modular circuit design in synthetic biology. We further note that while the best performance of the insulators are achieved when these act at a faster timescale than the upstream module (as typically required), it is not necessary for them to act on a faster timescale than the downstream module in our construction.