Qutub Amina A, Liu Gang, Vempati Prakash, Popel Aleksander S
Department of Biomedical Engineering, Johns Hopkins University, School of Medicine, 613 Traylor Bldg., 720 Rutland Ave, Baltimore, MD 21205, USA.
Pac Symp Biocomput. 2009:316-27.
Multiscale modeling has emerged as a powerful approach to interpret and capitalize on the biological complexity underlying blood vessel growth. We present a multiscale model of angiogenesis that heralds the start of a large scale initiative to integrate related biological models. The goal of the integrative project is to better understand underlying biological mechanisms from the molecular level up through the organ systems level, and test new therapeutic strategies. Model methodology includes ordinary and partial differential equations, stochastic models, complex logical rules, and agent-based architectures. Current modules represent blood flow, oxygen transport, growth factor distribution and signaling, cell sensing, cell movement and cell proliferation. Challenges of integration lie in connecting modules that are diversely designed, seamlessly coordinating feedback, and representing spatial and time scales from ligand-receptor interactions and intracellular signaling, to cell-level movement and cell-matrix interactions, to vessel branching and capillary network formation, to tissue level characteristics, to organ system response. We briefly introduce the individual modules, discuss our approach to integration, present initial results from the coordination of modules, and propose solutions to some critical issues facing angiogenesis multiscale modeling and integration.
多尺度建模已成为一种强大的方法，用于解释和利用血管生长背后的生物学复杂性。我们提出了一种血管生成的多尺度模型，这标志着一项整合相关生物学模型的大规模计划的开始。这个整合项目的目标是从分子水平到器官系统水平更好地理解潜在的生物学机制，并测试新的治疗策略。模型方法包括常微分方程和偏微分方程、随机模型、复杂逻辑规则以及基于主体的架构。当前的模块代表血流、氧气运输、生长因子分布与信号传导、细胞感知、细胞运动和细胞增殖。整合的挑战在于连接设计各异的模块、无缝协调反馈以及呈现从配体 - 受体相互作用和细胞内信号传导，到细胞水平运动和细胞 - 基质相互作用，再到血管分支和毛细血管网络形成，直至组织水平特征和器官系统反应的空间和时间尺度。我们简要介绍各个模块，讨论我们的整合方法，展示模块协调的初步结果，并提出解决血管生成多尺度建模与整合所面临的一些关键问题的方案。
