School of Biological Sciences, University of Bristol, Bristol, United Kingdom.
School of BioSciences, University of Melbourne, Melbourne, Victoria, Australia.
Biophys J. 2021 Apr 20;120(8):1314-1322. doi: 10.1016/j.bpj.2021.02.017. Epub 2021 Feb 20.
Understanding synchrony in growing populations is important for applications as diverse as epidemiology and cancer treatment. Recent experiments employing fluorescent reporters in melanoma cell lines have uncovered growing subpopulations exhibiting sustained oscillations, with nearby cells appearing to synchronize their cycles. In this study, we demonstrate that the behavior observed is consistent with long-lasting transient phenomenon initiated and amplified by the finite-sample effects and demographic noise. We present a novel mathematical analysis of a multistage model of cell growth, which accurately reproduces the synchronized oscillations. As part of the analysis, we elucidate the transient and asymptotic phases of the dynamics and derive an analytical formula to quantify the effect of demographic noise in the appearance of the oscillations. The implications of these findings are broad, such as providing insight into experimental protocols that are used to study the growth of asynchronous populations and, in particular, those investigations relating to anticancer drug discovery.
理解不断增长的群体中的同步性对于流行病学和癌症治疗等各种应用都很重要。最近的实验在黑色素瘤细胞系中使用荧光报告基因，揭示了不断增长的亚群表现出持续的振荡，附近的细胞似乎同步了它们的周期。在这项研究中，我们证明观察到的行为与由有限样本效应和人口噪声引发和放大的持久瞬态现象一致。我们提出了一个细胞生长多阶段模型的新的数学分析，该模型可以准确地再现同步振荡。作为分析的一部分，我们阐明了动力学的瞬态和渐近阶段，并推导出一个分析公式来量化人口噪声对振荡出现的影响。这些发现的意义很广泛，例如为研究异步群体生长的实验方案提供了深入的了解，特别是那些与抗癌药物发现相关的研究。
