We developed a multiscale model for simulating aggregation of multiple, free-flowing platelets in low–intermediate shear viscous flow, in which aggregation is mediated by the interaction of α_IIbβ₃ receptors on the platelet membrane and fibrinogen (Fg). This multiscale model uses coarse grained molecular dynamics (CGMD) for platelets at the microscales and dissipative particle dynamics (DPD) for the shear flow at the macroscales, employing our hybrid aggregation force field for modeling molecular level receptor ligand bonds. We define an aggregation tensor and use it to quantify the molecular level contact characteristics between platelets in an aggregate. We perform numerical studies under different flow conditions for platelet doublets and triplets and evaluate the contact area, detaching force and minimum distance between different pairs of platelets in an aggregate. We also present the dynamics of applied stress and velocity magnitude distributions on the platelet membrane during aggregation and quantify the increase in stress in the contact region under different flow conditions. Integrating the knowledge from our previously validated models, together with new aggregation scenarios, our model can dynamically quantify aggregation characteristics and map stress and velocity distribution on the platelet membrane which are difficult to measure in vitro, thus providing an insight into mechanotransduction bond formation response of platelets to flow-induced shear stresses. This modeling framework, together with the tensor method for quantifying inter-platelet contact, can be extended to simulate and analyze larger aggregates and their adhesive properties.

我们开发了一种多尺度模型，用于模拟低中剪切粘性流中多个自由流动血小板的聚集，其中聚集是由血小板膜上的 α _IIb β ₃受体与纤维蛋白原 (Fg) 的相互作用介导的。该多尺度模型对微观尺度的血小板使用粗粒分子动力学 (CGMD)，对宏观尺度的剪切流使用耗散粒子动力学 (DPD)，并采用我们的混合聚集力场来模拟分子水平受体配体键。我们定义了一个聚集张量，并用它来量化聚集体中血小板之间的分子水平接触特征。我们在不同的流动条件下对血小板双联体和三联体进行数值研究，并评估聚集体中不同血小板对之间的接触面积、分离力和最小距离。我们还展示了聚集过程中血小板膜上施加的应力和速度大小分布的动态，并量化了不同流动条件下接触区域的应力增加。整合我们之前验证的模型的知识以及新的聚集场景，我们的模型可以动态量化聚集特征并绘制血小板膜上难以在体外测量的应力和速度分布，从而深入了解血小板膜上的力转导键形成响应血小板对流动引起的剪切应力的影响。该建模框架与用于量化血小板间接触的张量方法一起可以扩展以模拟和分析更大的聚集体及其粘合特性。