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Robust in-phase synchronization in repressor-based coupled gene oscillators

机译：基于压缩耦合基因振荡器的鲁棒同步

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Inside living cells, proteins or mRNA can show oscillations even without a periodic driving force. Such genetic oscillations are precise timekeepers for cell-cycle regulations, pattern formation during embryonic development in higher animals, and daily cycle maintenance in most organisms. The synchronization between oscillations in adjacent cells happens via intercellular coupling, which is essential for periodic segmentation formation in vertebrates and other biological processes. While molecular mechanisms of generating sustained oscillations are quite well understood, how do simple intercellular coupling produces robust synchronizations are still poorly understood? To address this question, we investigate two models of coupled gene oscillators - activator-based coupled oscillators (ACO) and repressor-based coupled oscillators (RCO) models. In our study, a single autonomous oscillator (that operates in a single cell) is based on a negative feedback, which is delayed by intracellular dynamics of an intermediate species. For the ACO model (RCO), the repressor protein of one cell activates (represses) the production of another protein in the neighbouring cell after a intercellular time delay. We investigate the coupled models in the presence of intrinsic noise due to the inherent stochasticity of the biochemical reactions. We analyze the collective oscillations from stochastic trajectories in the presence and absence of explicit coupling delay and make careful comparison between two models. Our results show no clear synchronizations in the ACO model when the coupling time delay is zero. However, a non-zero coupling delay can lead to anti-phase synchronizations in ACO. Interestingly, the RCO model shows robust in-phase synchronizations in the presence and absence of the coupling time delay. Our results suggest that the naturally occurring intercellular couplings might be based on repression rather than activation where in-phase synchronization is crucial.
机译：在活细胞内，即使没有周期性驱动力，蛋白质或mRNA也可以显示振荡。这种遗传振荡是细胞周期法规的精确计时，在较高动物中胚胎发育期间的图案形成，以及大多数生物中的每日循环维持。相邻单元中的振荡之间的同步通过间细胞间耦合发生，这对于脊椎动物和其他生物过程中的周期性分割形成至关重要。虽然产生持续振荡的分子机制很好地理解，但是如何如何稳定地理解稳健同步的方式如何变得难以理解？为了解决这个问题，我们研究了两种耦合基因振荡器 - 激活因子的耦合振荡器（ACO）和基于阻遏的耦合振荡器（RCO）模型的模型。在我们的研究中，单个自主振荡器（在单个电池中操作）基于负反馈，其被中间物种的细胞内动态延迟。对于ACO模型（RCO），一种细胞的阻遏物蛋白激活（抑制）在细胞间延迟之后在相邻细胞中产生另一种蛋白质的产生。我们在存在由于生物化学反应的固有的随机性，在固有噪声存在下研究耦合模型。我们在存在和缺乏明确耦合延迟的情况下，在随机轨迹中分析集体振荡，并在两种模型之间进行仔细比较。我们的结果在耦合时间延迟为零时，ACO模型中没有明确同步。但是，非零耦合延迟可能导致ACO中的抗相同步。有趣的是，RCO模型在存在和不存在耦合时间延迟时显示了稳健的同步同步。我们的结果表明，天然存在的间细胞间耦合可能基于抑制而不是激活，其中同步同步至关重要。

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