A Multiscale Model for Recruitment Aggregation of Platelets by Correlating with In Vitro Results
A Multiscale Model for Recruitment Aggregation of Platelets by Correlating with In Vitro Results
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DOI：
10.1007/s12195-019-00583-2
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发表时间：
2019-08-01
影响因子：
2.8
通讯作者：
Deng, Yuefan
中科院分区：
文献类型：
--
作者：
Gupta, Prachi;Zhang, Peng;Deng, Yuefan
简介我们开发了一种多尺度模型，通过沉积在血管壁上的活化血小板招募在粘性剪切流中流动的未活化血小板来模拟血小板聚集的动力学。该模型对微观尺度的血小板使用粗粒分子动力学，对宏观尺度的剪切流使用耗散粒子动力学。在相对较低的剪切力条件下，纤维蛋白原通过 α IIb β 3 受体介导聚集。方法 α IIb β 3 和纤维蛋白原的结合通过分子水平混合力场建模，该力场分别由莫尔斯势和胡克定律组成，用于非键合和键合相互作用。通过与体外测量的血小板接触面积以及 α IIb β 3 和纤维蛋白原之间的分离力相关联，计算以两种不同相互作用尺度参数化的力场。结果使用我们的模型，通过整合剪切流中募集聚集过程中分子尺度的血小板间相互作用，得出募集力与两个血小板质心之间的距离之间的关系。我们的模型表明，与考虑血小板变形性的模型相比，假设刚性血小板模型会低估 89% 的接触面积和 93% 的分离力，从而预测招募过程中的附着力显着降低。结论我们的模型的分子水平预测能力揭示了瞬时和永久血小板聚集模式之间观察到的差异。该模型和模拟框架可以进一步适应模拟涉及多个流动血小板的初始血栓形成以及在血管上的沉积和粘附。
IntroductionWe developed a multiscale model to simulate the dynamics of platelet aggregation by recruitment of unactivated platelets flowing in viscous shear flows by an activated platelet deposited onto a blood vessel wall. This model uses coarse grained molecular dynamics for platelets at the microscale and dissipative particle dynamics for the shear flow at the macroscale. Under conditions of relatively low shear, aggregation is mediated by fibrinogen via alpha IIb beta 3 receptors.MethodsThe binding of alpha IIb beta 3 and fibrinogen is modeled by a molecular-level hybrid force field consisting of Morse potential and Hooke law for the nonbonded and bonded interactions, respectively. The force field, parametrized in two different interaction scales, is calculated by correlating with the platelet contact area measured in vitro and the detaching force between alpha IIb beta 3 and fibrinogen.ResultsUsing our model, we derived, the relationship between recruitment force and distance between the centers of mass of two platelets, by integrating the molecular-scale inter-platelet interactions during recruitment aggregation in shear flows. Our model indicates that assuming a rigid-platelet model, underestimates the contact area by 89% and the detaching force by 93% as compared to a model that takes into account the platelet deformability leading to a prediction of a significantly lower attachment during recruitment.ConclusionsThe molecular-level predictive capability of our model sheds a light on differences observed between transient and permanent platelet aggregation patterns. The model and simulation framework can be further adapted to simulate initial thrombus formation involving multiple flowing platelets as well as deposition and adhesion onto blood vessels.