Exploring the Underlying Mechanisms of the Xenopus laevis Embryonic Cell Cycle
Exploring the Underlying Mechanisms of the Xenopus laevis Embryonic Cell Cycle
复制标题
探索非洲爪蟾胚胎细胞周期的潜在机制
DOI：
10.1021/acs.jpcb.7b11840
复制
发表时间：
2018
影响因子：
3.3
通讯作者：
Wang Jin
中科院分区：
文献类型：
--
作者：
Zhang Kun;Wang Jin
细胞周期是增殖和发育中不可或缺的过程。尽管做出了重大努力，但全球量化和物理理解仍然具有挑战性。在这项研究中，我们探讨了非洲爪蟾胚胎细胞周期的机制，通过量化潜在的景观和流量。我们发现了非洲爪蟾胚胎细胞周期的墨西哥帽景观，在振荡路径上有几个局部盆地和障碍，局部盆地表征了非洲爪蟾胚胎细胞周期的不同阶段，局部障碍代表了检查点。景观盆地和屏障揭示了细胞周期的检查点机制。而景观形状决定了振荡路径上状态的稳定性，旋度通量力决定了细胞周期流的稳定性。复制是活细胞生物学的基础。我们将输入能量（通过熵产生）量化为单细胞生命（细胞周期）启动和持续的热力学要求。此外，我们还量化的卷曲通量起源于输入能量的动力学要求出现一个新的稳定相（细胞周期）。这可以为单细胞生命的起源提供新的定量见解。事实上，来自能量输入或营养供应的卷曲通量决定了细胞周期的速度并保证了细胞周期的进展。细胞周期的速度是癌症的标志。我们的特点是质量的细胞周期的相干时间，并发现它是支持的通量和能量成本。我们还能够量化的时间不可逆性的程度由互相关函数向前和向后的时间从随机轨迹在模拟或实验，提供了一种方法的量化的时间不可逆性和流量。通过对景观和通量的全局敏感性分析，我们可以确定控制细胞周期速度的关键因素。这可以帮助设计一种有效的抗癌药物发现策略。
The cell cycle is an indispensable process in proliferation and development. Despite significant efforts, global quantification and physical understanding are still challenging. In this study, we explored the mechanisms of theXenopus laevisembryonic cell cycle by quantifying the underlying landscape and flux. We uncovered the Mexican hat landscape of theXenopus laevisembryonic cell cycle with several local basins and barriers on the oscillation path. The local basins characterize the different phases of theXenopus laevisembryonic cell cycle, and the local barriers represent the checkpoints. The checkpoint mechanism of the cell cycle is revealed by the landscape basins and barriers. While landscape shape determines the stabilities of the states on the oscillation path, the curl flux force determines the stability of the cell cycle flow. Replication is fundamental for biology of living cells. We quantify the input energy (through the entropy production) as the thermodynamic requirement for initiation and sustainability of single cell life (cell cycle). Furthermore, we also quantify curl flux originated from the input energy as the dynamical requirement for the emergence of a new stable phase (cell cycle). This can provide a new quantitative insight for the origin of single cell life. In fact, the curl flux originated from the energy input or nutrition supply determines the speed and guarantees the progression of the cell cycle. The speed of the cell cycle is a hallmark of cancer. We characterized the quality of the cell cycle by the coherence time and found it is supported by the flux and energy cost. We are also able to quantify the degree of time irreversibility by the cross correlation function forward and backward in time from the stochastic traces in the simulation or experiments, providing a way for the quantification of the time irreversibility and the flux. Through global sensitivity analysis upon landscape and flux, we can identify the key elements for controlling the cell cycle speed. This can help to design an effective strategy for drug discovery against cancer.