Bhalla Upinder S., Iyengar Ravi
National Centre for Biological Sciences, Bangalore 560065, India.
Chaos. 2001 Mar;11(1):221-226. doi: 10.1063/1.1350440.
Biological signaling networks comprised of cellular components including signaling proteins and small molecule messengers control the many cell function in responses to various extracellular and intracellular signals including hormone and neurotransmitter inputs, and genetic events. Many signaling pathways have motifs familiar to electronics and control theory design. Feedback loops are among the most common of these. Using experimentally derived parameters, we modeled a positive feedback loop in signaling pathways used by growth factors to trigger cell proliferation. This feedback loop is bistable under physiological conditions, although the system can move to a monostable state as well. We find that bistability persists under a wide range of regulatory conditions, even when core enzymes in the feedback loop deviate from physiological values. We did not observe any other phenomena in the core feedback loop, but the addition of a delayed inhibitory feedback was able to generate oscillations under rather extreme parameter conditions. Such oscillations may not be of physiological relevance. We propose that the kinetic properties of this feedback loop have evolved to support bistability and flexibility in going between bistable and monostable modes, while simultaneously being very refractory to oscillatory states. (c) 2001 American Institute of Physics.
由信号蛋白和小分子信使等细胞成分组成的生物信号网络，可响应包括激素和神经递质输入以及基因事件在内的各种细胞外和细胞内信号，从而控制多种细胞功能。许多信号通路具有电子学和控制理论设计中常见的基序。反馈回路就是其中最常见的一种。利用实验得出的参数，我们对生长因子用于触发细胞增殖的信号通路中的正反馈回路进行了建模。尽管该系统也能转变为单稳态，但在生理条件下，这个反馈回路是双稳态的。我们发现，即使反馈回路中的核心酶偏离生理值，双稳态在广泛的调节条件下依然存在。在核心反馈回路中，我们未观察到任何其他现象，但添加延迟抑制性反馈能够在相当极端的参数条件下产生振荡。这种振荡可能与生理无关。我们认为，该反馈回路的动力学特性已经进化，以支持双稳态以及在双稳态和单稳态模式之间转换的灵活性，同时对振荡状态具有很强的抗性。（c）2001美国物理研究所。
