Department of Surgery, The University of Chicago, Chicago, Illinois 60622, USA.
Wound Repair Regen. 2012 Nov-Dec;20(6):862-71. doi: 10.1111/j.1524-475X.2012.00852.x. Epub 2012 Oct 30.
Damage to an epithelial surface disrupts its mechanical and immunologic barrier function and exposes underlying tissues to a potentially hostile external environment. Epithelial restitution occurs quickly to reestablish the barrier and comprises a major part of the immediate host response to injured tissue. Pathways involving transforming growth factor beta and activation of epidermal growth factor receptor are both of critical importance, although cross-pathway interactions have been poorly characterized. Agent-based modeling has been showed to be useful in integrating disparate bodies of knowledge and showing the dynamic consequences of pathway structures and cellular population behavior and is used herein to create an in silico analog of an in vitro scratch assay. The In Vitro Scratch Agent-Based Model consists of agents representing individual epithelial cells in a simulated extracellular matrix. Agents sense signals from the damaged environment and produce effector molecules, leading to their healing behavior. The In Vitro Scratch Agent-Based Model qualitatively matched wound healing dynamics when compared against data from traditional experiments. Putative cross-talk mechanisms were then instantiated into the In Vitro Scratch Agent-Based Model and their relative plausibility examined, suggesting interaction at the receptor tyrosine kinase level. This highlights the utility of dynamic knowledge representation in the integration of pathways previously studied in separate contexts.
上皮表面的损伤会破坏其机械和免疫屏障功能，使下面的组织暴露在潜在的恶劣外部环境中。上皮修复会迅速发生，以重新建立屏障，这是组织损伤后宿主即刻反应的主要部分。涉及转化生长因子β和表皮生长因子受体激活的途径都非常重要，尽管交叉途径相互作用的特征描述较差。基于代理的建模已被证明在整合不同的知识体系和展示途径结构和细胞群体行为的动态后果方面非常有用，本文使用它来创建体外划痕测定的计算机模拟。体外划痕基于代理的模型由代表模拟细胞外基质中单个上皮细胞的代理组成。代理感知来自受损环境的信号，并产生效应分子，从而导致它们的愈合行为。与传统实验相比，体外划痕基于代理的模型在定性上匹配了伤口愈合动力学。然后将假定的交叉对话机制实例化到体外划痕基于代理的模型中，并检查其相对合理性，表明在受体酪氨酸激酶水平上存在相互作用。这突出了动态知识表示在整合先前在不同上下文中研究的途径方面的实用性。
