Michael A Kochen, Joseph L Hellerstein, Herbert M Sauro
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引用次数: 0
Abstract
Cellular signal transduction takes place through a network of phosphorylation cycles. These pathways take the form of a multi-layered cascade of cycles. This work focuses on the sensitivity of single, double and n length cycles. Cycles that operate in the zero-order regime can become sensitive to changes in signal, resulting in zero-order ultrasensitivity (ZOU). Using frequency analysis, we confirm previous efforts that cascades can act as noise filters by computing the bandwidth. We show that n length cycles display what we term first-order ultrasensitivity which occurs even when the cycles are not operating in the zero-order regime. The magnitude of the sensitivity, however, has an upper bound equal to the number of cycles. It is known that ZOU can be significantly reduced in the presence of retroactivity. We show that the first-order ultrasensitivity is immune to retroactivity and that the ZOU and first-order ultrasensitivity can be blended to create systems with constant sensitivity over a wider range of signal. We show that the ZOU in a double cycle is only modestly higher compared with a single cycle. We therefore speculate that the double cycle has evolved to enable amplification even in the face of retroactivity.
细胞信号传导是通过磷酸化循环网络进行的。这些途径以多层级联循环的形式出现。这项工作的重点是单长、双长和 n 长循环的敏感性。在零阶机制下运行的循环会对信号的变化变得敏感,从而产生零阶超灵敏度(ZOU)。通过频率分析,我们证实了之前的研究成果,即级联可以通过计算带宽起到噪声滤波器的作用。我们的研究表明,n 个长度的循环显示出我们所称的一阶超灵敏度,即使循环不在零阶系统中运行,这种超灵敏度也会出现。然而,灵敏度的大小有一个与周期数相等的上限。众所周知,在存在追溯性的情况下,ZOU 可以显著降低。我们的研究表明,一阶超灵敏度不受追溯性的影响,而且 ZOU 和一阶超灵敏度可以混合使用,以创建在更大信号范围内灵敏度恒定的系统。我们的研究表明,与单周期相比,双周期的 ZOU 只略微高一些。因此,我们推测,双循环的进化是为了即使在逆反应的情况下也能实现放大。
期刊介绍:
Each Interface Focus themed issue is devoted to a particular subject at the interface of the physical and life sciences. Formed of high-quality articles, they aim to facilitate cross-disciplinary research across this traditional divide by acting as a forum accessible to all. Topics may be newly emerging areas of research or dynamic aspects of more established fields. Organisers of each Interface Focus are strongly encouraged to contextualise the journal within their chosen subject.