细胞分裂周期是在多细胞发育过程中表现出高度可塑性的基本生理过程。这种可塑性在从早期胚胎的快速和严格定时分裂到随后的大小控制的有丝分裂周期的过渡中很明显。在后来的发展中,细胞可能会暂停并重新开始增殖,以响应无数的内部或外部信号,或在终末分化或衰老后永久退出细胞周期。除此之外,细胞可以经历修改的细胞分裂变体,比如内复制,这增加了它们的倍性,或者减数分裂,这降低了它们的倍性。这种丰富的行为导致了许多概念性的类比,旨在作为理解增殖程序的框架。这里,我们的目标是将这些机制统一在一个动态范式下。为此,我们采用控制理论方法将细胞周期框架为一对可阻止和相互抑制的,双重放大,负反馈振荡器控制染色体复制和分离事件,分别。在适当的条件下,这个框架可以重现固定周期的振荡,不同持续时间的检查站逮捕,和内膜。随后,我们使用相平面和分岔分析来解释这些性质的动力学基础。然后,使用生理上现实的,生化模型,我们表明,相同的调控结构支撑着细胞周期控制网络的不同功能。我们得出的结论是,牛顿的摇篮可能是细胞周期调节方式的合适机械类比。
The cell division cycle is a fundamental physiological process displaying a great degree of plasticity during the course of multicellular development. This plasticity is evident in the transition from rapid and stringently-timed divisions of the early embryo to subsequent size-controlled mitotic cycles. Later in development, cells may pause and restart proliferation in response to myriads of internal or external signals, or permanently exit the cell cycle following terminal differentiation or senescence. Beyond this, cells can undergo modified cell division variants, such as endoreplication, which increases their ploidy, or meiosis, which reduces their ploidy. This wealth of behaviours has led to numerous conceptual analogies intended as frameworks for understanding the proliferative program. Here, we aim to unify these mechanisms under one dynamical paradigm. To this end, we take a control theoretical approach to frame the cell cycle as a pair of arrestable and mutually-inhibiting, doubly amplified, negative feedback oscillators controlling chromosome replication and segregation events, respectively. Under appropriate conditions, this framework can reproduce fixed-period oscillations, checkpoint arrests of variable duration, and endocycles. Subsequently, we use phase plane and bifurcation analysis to explain the dynamical basis of these properties. Then, using a physiologically realistic, biochemical model, we show that the very same regulatory structure underpins the diverse functions of the cell cycle control network. We conclude that Newton\'s cradle may be a suitable mechanical analogy of how the cell cycle is regulated.