Multi-cell agent-based simulation of the microvasculature to study the dynamics of circulating inflammatory cell trafficking
Multi-cell agent-based simulation of the microvasculature to study the dynamics of circulating inflammatory cell trafficking
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DOI：
10.1007/s10439-007-9266-1
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发表时间：
2007-06-01
影响因子：
3.8
通讯作者：
Peirce, Shayn M.
中科院分区：
文献类型：
--
作者：
Bailey, Alexander M.;Thorne, Bryan C.;Peirce, Shayn M.
白细胞通过微循环进入组织是血管生成、炎症和免疫反应的核心。虽然文献中有丰富的描述这些过程的分子介质的机制细节，但信号事件和细胞行为在一个单位内的整合。需要多细胞组织水平的艾德空间和时间框架来实现更全面的理解。我们已经开发出一种新的计算框架，结合基于代理的建模（ABM）与网络。分析以研究单核细胞归巢。将来自小鼠肌肉的微血管网络结构并入ABM中。在模拟中，每个单独的细胞由单独的代理代表。网络。OW模型计算整个模拟微血管网络的血液动力学参数（血流速率、流体剪切应力和流体静压）。这些被并入ABM以影响单核细胞通过网络的转运和趋化因子/细胞因子浓度。反过来，模拟单核细胞响应其局部机械和生化环境，并根据来自独立文献的规则集做出行为决策。模拟的细胞行为引起紧急的白细胞滚动、粘附和外渗。进行分子敲除模拟以验证模型，并且单核细胞粘附、滚动和外渗的预测与独立发表的相应小鼠研究显示出良好的一致性。
Leukocyte trafficking through the microcirculation and into tissues is central in angiogenesis, inflammation, and the immune response. Although the literature is rich with mechanistic detail describing molecular mediators of these processes, integration of signaling events and cell behaviors within a uni. ed spatial and temporal framework at the multicell tissue-level is needed to achieve a fuller understanding. We have developed a novel computational framework that combines agent-based modeling (ABM) with a network. ow analysis to study monocyte homing. A microvascular network architecture derived from mouse muscle was incorporated into the ABM. Each individual cell was represented by an individual agent in the simulation. The network. ow model calculates hemodynamic parameters (blood flow rates, fluid shear stress, and hydrostatic pressures) throughout the simulated microvascular network. These are incorporated into the ABM to affect monocyte transit through the network and chemokine/cytokine concentrations. In turn, simulated monocytes respond to their local mechanical and biochemical environments and make behavioral decisions based on a rule set derived from independent literature. Simulated cell behaviors give rise to emergent leukocyte rolling, adhesion, and extravasation. Molecular knockout simulations were performed to validate the model, and predictions of monocyte adhesion, rolling, and extravasation show good agreement with the independently published corresponding mouse studies.