Introduction

We 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 αIIbβ3 receptors.

Methods

The binding of αIIbβ3 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 αIIbβ3 and fibrinogen.

Results

Using 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.

Conclusions

The 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.

中文翻译：

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通过与体外结果相关的血小板募集聚集的多尺度模型。

介绍

我们开发了一个多尺度模型，通过沉积在血管壁上的活化血小板募集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。在相对低剪切的条件下，聚集是由纤维蛋白原通过αIIbβ3 受体介导的。

方法

αIIbβ3 和纤维蛋白原的结合由分子水平的混合力场建模，该混合力场由莫尔斯势和胡克定律组成，分别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和 αIIbβ3 与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，我们通过整合剪切流中募集聚集期间的分子级血小板间相互作用，推导出募集力和两个血小板质心之间的距离之间的关系。我们的模型表明，假设一个刚性血小板模型，与考虑血小板变形性的模型相比，低估了 89% 的接触面积和 93% 的分离力，导致预测在募集期间的附着显着降低。

结论

我们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用于模拟涉及多个流动血小板的初始血栓形成以及血管上的沉积和粘附。