Kim Jongrae, Heslop-Harrison Pat, Postlethwaite Ian, Bates Declan G
Control and Instrumentation Group, Department of Engineering, University of Leicester, Leicester, United Kingdom.
PLoS Comput Biol. 2007 Nov;3(11):e218. doi: 10.1371/journal.pcbi.0030218. Epub 2007 Sep 26.
Stable and robust oscillations in the concentration of adenosine 3', 5'-cyclic monophosphate (cAMP) are observed during the aggregation phase of starvation-induced development in Dictyostelium discoideum. In this paper we use mathematical modelling together with ideas from robust control theory to identify two factors which appear to make crucial contributions to ensuring the robustness of these oscillations. Firstly, we show that stochastic fluctuations in the molecular interactions play an important role in preserving stable oscillations in the face of variations in the kinetics of the intracellular network. Secondly, we show that synchronisation of the aggregating cells through the diffusion of extracellular cAMP is a key factor in ensuring robustness of the oscillatory waves of cAMP observed in Dictyostelium cell cultures to cell-to-cell variations. A striking and quite general implication of the results is that the robustness analysis of models of oscillating biomolecular networks (circadian clocks, Ca(2+) oscillations, etc.) can only be done reliably by using stochastic simulations, even in the case where molecular concentrations are very high.
在盘基网柄菌饥饿诱导发育的聚集阶段，可观察到3',5'-环磷酸腺苷（cAMP）浓度的稳定且强劲的振荡。在本文中，我们运用数学建模并结合鲁棒控制理论的思想，来确定两个似乎对确保这些振荡的鲁棒性起着关键作用的因素。首先，我们表明分子相互作用中的随机波动在面对细胞内网络动力学变化时，对维持稳定振荡起着重要作用。其次，我们表明通过细胞外cAMP的扩散使聚集细胞同步，是确保在盘基网柄菌细胞培养物中观察到的cAMP振荡波对细胞间差异具有鲁棒性的关键因素。这些结果一个显著且相当普遍的含义是，即使在分子浓度非常高的情况下，振荡生物分子网络（生物钟、Ca(2+)振荡等）模型的鲁棒性分析也只能通过使用随机模拟来可靠地完成。
