当前位置: X-MOL 学术Phys. Life Rev. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Modeling thrombosis in silico: Frontiers, challenges, unresolved problems and milestones
Physics of Life Reviews ( IF 13.7 ) Pub Date : 2018-03-05 , DOI: 10.1016/j.plrev.2018.02.005
A.V. Belyaev , J.L. Dunster , J.M. Gibbins , M.A. Panteleev , V. Volpert

Hemostasis is a complex physiological mechanism that functions to maintain vascular integrity under any conditions. Its primary components are blood platelets and a coagulation network that interact to form the hemostatic plug, a combination of cell aggregate and gelatinous fibrin clot that stops bleeding upon vascular injury. Disorders of hemostasis result in bleeding or thrombosis, and are the major immediate cause of mortality and morbidity in the world. Regulation of hemostasis and thrombosis is immensely complex, as it depends on blood cell adhesion and mechanics, hydrodynamics and mass transport of various species, huge signal transduction networks in platelets, as well as spatiotemporal regulation of the blood coagulation network. Mathematical and computational modeling has been increasingly used to gain insight into this complexity over the last 30 years, but the limitations of the existing models remain profound. Here we review state-of-the-art-methods for computational modeling of thrombosis with the specific focus on the analysis of unresolved challenges. They include: a) fundamental issues related to physics of platelet aggregates and fibrin gels; b) computational challenges and limitations for solution of the models that combine cell adhesion, hydrodynamics and chemistry; c) biological mysteries and unknown parameters of processes; d) biophysical complexities of the spatiotemporal networks' regulation. Both relatively classical approaches and innovative computational techniques for their solution are considered; the subjects discussed with relation to thrombosis modeling include coarse-graining, continuum versus particle-based modeling, multiscale models, hybrid models, parameter estimation and others. Fundamental understanding gained from theoretical models are highlighted and a description of future prospects in the field and the nearest possible aims are given.



中文翻译:

模拟计算机中的血栓形成:前沿,挑战,未解决的问题和里程碑

止血是一种复杂的生理机制,可在任何情况下维持血管完整性。它的主要成分是血小板和凝血网络,它们相互作用形成止血栓,这是细胞聚集体和凝胶状纤维蛋白凝块的组合,可在血管损伤后停止出血。止血失调导致出血或血栓形成,并且是世界范围内死亡率和发病率的主要直接原因。止血和血栓形成的调节非常复杂,因为它取决于血细胞的粘附和力学,各种物种的流体动力学和质量传递,血小板中巨大的信号转导网络以及凝血网络的时空调节。在过去的30年中,越来越多地使用数学和计算模型来了解这种复杂性,但是现有模型的局限性仍然很深。在这里,我们回顾了血栓形成的计算模型的最新方法,特别侧重于未解决挑战的分析。它们包括:a)与血小板聚集体和纤维蛋白凝胶的物理学有关的基本问题;b)结合细胞粘附,流体动力学和化学的模型求解的计算挑战和局限性;c)生物学的奥秘和未知的过程参数;d)时空网络调控的生物物理复杂性。既考虑了相对经典的方法,又考虑了创新的计算技术来解决问题;与血栓形成模型相关的讨论主题包括粗粒度,连续体与基于粒子的模型,多尺度模型,混合模型,参数估计等。强调了从理论模型中获得的基本理解,并描述了该领域的未来前景和最接近的目标。

更新日期:2018-03-05
down
wechat
bug