Qu Zhilin, Weiss James N, MacLellan W Robb
Cardiovascular Research Laboratory, University of California, 10833 Le Conte Avenue, Los Angeles, California 90095, USA.
J Cell Sci. 2004 Aug 15;117(Pt 18):4199-207. doi: 10.1242/jcs.01294. Epub 2004 Jul 27.
Although there is general agreement that cell growth and division are functionally coordinated, the mechanisms that link the two processes are poorly understood. In this study, we have developed a mathematical model based on current biological concepts of the signaling transduction pathways involved in cell growth, which predicts that cell growth rate is proportional to cell surface area at birth. To investigate the relationship between growth control and cell division, we then applied our mathematical model to three classic experiments measuring cycle time versus cell birth size in fission yeast and Xenopus laevis, and the cell cycle delay in mammalian cells after serum withdrawal. When coupled to a cell cycle exhibiting 'sizer' and 'timer' phases, we show that a simple model in which growth rate is proportional to the cell surface area immediately after division reproduces the experimental observations including the relationship between cycle time and birth size in fission yeast and Xenopus laevis. The model also accounts for the cell cycle delay seen in restriction point experiments performed in HeLa cells.
尽管人们普遍认为细胞生长和分裂在功能上是协调的，但连接这两个过程的机制却知之甚少。在本研究中，我们基于当前关于细胞生长中信号转导途径的生物学概念开发了一个数学模型，该模型预测细胞生长速率与出生时的细胞表面积成正比。为了研究生长控制与细胞分裂之间的关系，我们随后将我们的数学模型应用于三个经典实验，这些实验测量了裂殖酵母和非洲爪蟾中细胞周期时间与细胞出生大小的关系，以及血清撤出后哺乳动物细胞中的细胞周期延迟。当与表现出“大小调控器”和“时间调控器”阶段的细胞周期相结合时，我们表明一个简单的模型，即生长速率与分裂后立即的细胞表面积成正比，能够重现实验观察结果，包括裂殖酵母和非洲爪蟾中细胞周期时间与出生大小之间的关系。该模型还解释了在HeLa细胞中进行的限制点实验中观察到的细胞周期延迟。
