论文标题
细胞增殖中加法机制的PDE模型
PDE models of adder mechanisms in cellular proliferation
论文作者
论文摘要
细胞分裂是一个涉及许多生化步骤和复杂生物物理机制的过程。为了简化对触发细胞分裂的理解,已经提出了与细胞分裂相关的更多微观细胞过程的三个基本模型。细胞可以根据其出生以来经过的时间,大小和/或添加的体积(分别是计时器,Sizer和Adder模型)来分裂。在这里,我们提出了统一的加法器模型,并研究了在细胞增殖中产生的不同加法过程的某些特性。尽管Adder-Sizer模型提供了一种模拟细胞种群结构的直接方法,但我们说明了它与细胞分裂依赖年龄和大小的众所周知模型的数学相关性。证明了对我们2+1维PDE模型的弱解决方案的存在和独特性,从而导致离散的数值溶液的收敛性,并使我们能够数值计算细胞群体密度的动态。然后,我们将PDE模型概括为结合了在细胞生长速率中表现出母女相关性的系统的最新实验发现。数值实验说明了可能的平均细胞体积爆炸以及与母女相关生长速率的细胞群体的动态行为。最后,以新的实验发现的启发,我们扩展了加法模型案例,其中控制变量是细胞周期中DNA复制起始点之间的附加大小。
Cell division is a process that involves many biochemical steps and complex biophysical mechanisms. To simplify the understanding of what triggers cell division, three basic models that subsume more microscopic cellular processes associated with cell division have been proposed. Cells can divide based on the time elapsed since their birth, their size, and/or the volume added since their birth -- the timer, sizer, and adder models, respectively. Here, we propose unified adder-sizer models and investigate some of the properties of different adder processes arising in cellular proliferation. Although the adder-sizer model provides a direct way to model cell population structure, we illustrate how it is mathematically related to the well-known model in which cell division depends on age and size. Existence and uniqueness of weak solutions to our 2+1-dimensional PDE model are proved, leading to the convergence of the discretized numerical solutions and allowing us to numerically compute the dynamics of cell population densities. We then generalize our PDE model to incorporate recent experimental findings of a system exhibiting mother-daughter correlations in cellular growth rates. Numerical experiments illustrating possible average cell volume blowup and the dynamical behavior of cell populations with mother-daughter correlated growth rates are carried out. Finally, motivated by new experimental findings, we extend our adder model cases where the controlling variable is the added size between DNA replication initiation points in the cell cycle.