Wang Ruiqi, Chen Luonan, Aihara Kazuyuki
Aihara Complexity Modelling Project, ERATO, JST, 4-6-1 Komaba, Meguro, Tokyo 153-8505, Japan.
Bioinformatics. 2006 Jul 15;22(14):1775-81. doi: 10.1093/bioinformatics/btl182. Epub 2006 May 11.
Although there are significant advances on elucidating the collective behaviors on biological organisms in recent years, the essential mechanisms by which the collective rhythms arise remain to be fully understood, and further how to synchronize multicellular networks by artificial control strategy has not yet been well explored.
A control strategy is developed to synchronize gene regulatory networks in a multicellular system when spontaneous synchronization cannot be achieved. We first construct an impulsive control system to model the process of periodically injecting coupling substances with constant or random impulsive control amounts into the common extracellular medium, and further study its effects on the dynamics of individual cells. We derive the threshold of synchronization induced by the periodic substance input. Therefore, we can synchronize the multicellular network to a specific collective behavior by changing the frequency and amplitude of the periodic stimuli. Moreover, a two-stage scheme is proposed to facilitate the synchronization in this paper. We show that the presence of the external input may also initiate different dynamics. The multicellular network of coupled repressilators is used to show the effectiveness of the proposed method. The results not only provide a perspective to understand the interactions between external stimuli and intrinsic physiological rhythms, but also may lead to development of realistic artificial control strategy and medical therapy.
尽管近年来在阐明生物有机体的集体行为方面取得了重大进展，但集体节律产生的基本机制仍有待充分理解，而且如何通过人工控制策略同步多细胞网络尚未得到充分探索。
当无法实现自发同步时，我们开发了一种控制策略来同步多细胞系统中的基因调控网络。我们首先构建一个脉冲控制系统，以模拟向共同的细胞外培养基中定期注入具有恒定或随机脉冲控制量的耦合物质的过程，并进一步研究其对单个细胞动力学的影响。我们推导了周期性物质输入诱导同步的阈值。因此，我们可以通过改变周期性刺激的频率和幅度将多细胞网络同步到特定的集体行为。此外，本文提出了一种两阶段方案来促进同步。我们表明外部输入的存在也可能引发不同的动力学。使用耦合抑制振荡器的多细胞网络来展示所提出方法的有效性。这些结果不仅为理解外部刺激与内在生理节律之间的相互作用提供了一个视角，而且可能导致现实的人工控制策略和医学治疗的发展。
aihara@sat.t.u - tokyo.ac.jp
