Institute of Biochemical Engineering and Center Systems Biology, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
Adv Biochem Eng Biotechnol. 2010;121:23-43. doi: 10.1007/10_2009_53.
Agent-based models are rigorous tools for simulating the interactions of individual entities, such as organisms or molecules within cells and assessing their effects on the dynamic behavior of the system as a whole. In context with bioprocess and biosystems engineering there are several interesting and important applications. This contribution aims at introducing this strategy with the aid of two examples characterized by striking distinctions in the scale of the individual entities and the mode of their interactions. In the first example a structured-segregated model is applied to travel along the lifelines of single cells in the environment of a three-dimensional turbulent field of a stirred bioreactor. The modeling approach is based on an Euler-Lagrange formulation of the system. The strategy permits one to account for the heterogeneity present in real reactors in both the fluid and cellular phases, respectively. The individual response of the cells to local variations in the extracellular concentrations is pictured by a dynamically structured model of the key reactions of the central metabolism. The approach permits analysis of the lifelines of individual cells in space and time.The second application of the individual modeling approach deals with dynamic modeling of signal transduction pathways in individual cells. Usually signal transduction networks are portrayed as being wired together in a spatially defined manner. Living circuitry, however, is placed in highly malleable internal architecture. Creating a homogenous bag of molecules, a well-mixed system, the dynamic behavior of which is modeled with a set of ordinary differential equations is normally not valid. The dynamics of the MAP kinase and a steroid hormone pathway serve as examples to illustrate how single molecule tracking can be linked with the stochasticity of biochemical reactions, where diffusion and reaction occur in a probabilistic manner. The problem of hindered diffusion caused by macromolecular crowding is also taken into account.
基于主体的模型是一种严谨的工具，可用于模拟个体实体（如细胞内的生物体或分子）之间的相互作用，并评估它们对整个系统动态行为的影响。在生物过程和生物系统工程中，有几个有趣且重要的应用。本贡献旨在借助两个示例来介绍这种策略，这两个示例在个体实体的规模和相互作用模式方面存在显著差异。在第一个示例中，采用结构化分离模型来沿着单个细胞在搅拌生物反应器三维湍流场环境中的生命线行进。该建模方法基于系统的欧拉-拉格朗日公式。该策略允许分别考虑真实反应器中流体相和细胞相中的异质性。细胞对细胞外浓度局部变化的个体反应由中心代谢关键反应的动态结构化模型描绘。该方法允许分析单个细胞在空间和时间上的生命线。个体建模方法的第二个应用涉及单个细胞中信号转导途径的动态建模。通常，信号转导网络以空间定义的方式描绘为相互连接。然而，活体电路位于高度可塑的内部结构中。创建一个同质的分子袋，一个充分混合的系统，其动态行为用一组常微分方程进行建模通常是无效的。MAP 激酶和类固醇激素途径的动力学作为示例，说明了如何将单个分子跟踪与生化反应的随机性联系起来，其中扩散和反应以概率方式发生。还考虑了由于大分子拥挤引起的扩散受阻问题。
