Spatial modeling of cell signaling networks.
Spatial modeling of cell signaling networks.
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DOI：
10.1016/b978-0-12-388403-9.00008-4
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发表时间：
2012
影响因子：
--
通讯作者：
Loew, Leslie M.
中科院分区：
文献类型：
--
作者：
Cowan, Ann E.;Moraru, Ion I.;Schaff, James C.;Slepchenko, Boris M.;Loew, Leslie M.
细胞的形状，亚细胞区室的大小和细胞质内分子的空间分布都可以控制分子如何相互作用以产生细胞行为。本章介绍了如何将这些空间特征纳入细胞信号传导的机械数学模型。Virtual Cell计算建模和模拟软件用于说明构建空间模型所需的考虑因素。解释如何适当地选择物理配方之间的隐含或明确的细胞几何形状和确定性与随机分子动力学配方之间，沿着讨论各自的优势和劣势。作为构建空间模型的第一步，需要指定几何形状，并将其与网络的分子、反应和膜通量过程相关联。初始条件、扩散系数、速度和边界条件完成了定义模型数学所需的规范。用于解决反应扩散问题的确定性和随机性的数值方法，然后描述，并提供了一些指导，在如何设置和运行模拟。本章结束时，对神经元中cAMP信号的研究提供了一个例子，说明通过应用空间建模可以解释实验结果。
The shape of a cell, the sizes of subcellular compartments and the spatial distribution of molecules within the cytoplasm can all control how molecules interact to produce a cellular behavior. This chapter describes how these spatial features can be included in mechanistic mathematical models of cell signaling. The Virtual Cell computational modeling and simulation software is used to illustrate the considerations required to build a spatial model. An explanation of how to appropriately choose between physical formulations that implicitly or explicitly account for cell geometry and between deterministic vs, stochastic formulations for molecular dynamics is provided, along with a discussion of their respective strengths and weaknesses. As a first step toward constructing a spatial model, the geometry needs to be specified and associated with the molecules, reactions and membrane flux processes of the network. Initial conditions, diffusion coefficients, velocities and boundary conditions complete the specifications required to define the mathematics of the model. The numerical methods used to solve reaction-diffusion problems both deterministically and stochastically are then described and some guidance is provided in how to set up and run simulations. A study of cAMP signaling in neurons ends the chapter, providing an example of the insights that can be gained in interpreting experimental results through the application of spatial modeling.