INRIA Paris-Rocquencourt, Domaine de Voluceau, Rocquencourt, B.P. 105, F-78153 Le Chesnay Cedex, France.
Math Biosci Eng. 2013 Feb;10(1):1-17. doi: 10.3934/mbe.2013.10.1.
Cell proliferation is controlled by many complex regulatory networks. Our purpose is to analyse, through mathematical modeling, the effects of growth factors on the dynamics of the division cycle in cell populations. Our work is based on an age-structured PDE model of the cell division cycle within a population of cells in a common tissue. Cell proliferation is at its first stages exponential and is thus characterised by its growth exponent, the first eigenvalue of the linear system we consider here, a growth exponent that we will explicitly evaluate from biological data. Moreover, this study relies on recent and innovative imaging data (fluorescence microscopy) that make us able to experimentally determine the parameters of the model and to validate numerical results. This model has allowed us to study the degree of simultaneity of phase transitions within a proliferating cell population and to analyse the role of an increased growth factor concentration in this process. This study thus aims at helping biologists to elicit the impact of growth factor concentration on cell cycle regulation, at making more precise the dynamics of key mechanisms controlling the division cycle in proliferating cell populations, and eventually at establishing theoretical bases for optimised combined anticancer treatments.
细胞增殖受许多复杂的调控网络控制。我们的目的是通过数学建模分析生长因子对细胞群体分裂周期动力学的影响。我们的工作基于一个细胞分裂周期的年龄结构偏微分方程模型,该模型适用于共同组织中的细胞群体。细胞增殖的最初阶段是指数级的,因此其生长指数是我们这里考虑的线性系统的第一个特征值,我们将根据生物数据明确评估该生长指数。此外,这项研究依赖于最近的创新成像数据(荧光显微镜),使我们能够通过实验确定模型的参数并验证数值结果。该模型使我们能够研究增殖细胞群体中相变的同步程度,并分析生长因子浓度增加在该过程中的作用。因此,这项研究旨在帮助生物学家了解生长因子浓度对细胞周期调控的影响,更精确地描述控制增殖细胞群体分裂周期的关键机制的动力学,并最终为优化联合抗癌治疗建立理论基础。