Laboratory of Optics and Dynamics of Biological Systems, Novosibirsk State University, Novosibirsk, Russia.
Laboratory of Photoactivatable Processes, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, Novosibirsk, Russia.
PLoS One. 2024 Oct 3;19(10):e0308679. doi: 10.1371/journal.pone.0308679. eCollection 2024.
Disorders of hemostasis resulting in bleeding or thrombosis are leading cause of mortality in the world. Blood platelets are main players in hemostasis, providing the primary response to the vessel wall injury. In this case, they rapidly switch to the activated state in reaction to the exposed chemical substances such as ADP, collagen and thrombin. Molecular mechanisms of platelet activation are known, and detailed computational models are available. However, they are too complicated for large-scale problems (e.g. simulation of the thrombus growth) where less detailed models are required, which still should take into account the variation of agonist concentration and heterogeneity of platelets. In this paper, we present a simple model of the platelet population response to a spatially inhomogeneous stimulus. First, computational nodes modeling platelets are placed randomly in space. Each platelet is assigned the specific threshold for agonist, which determines whether it becomes activated at a given time. The distribution of the threshold value in a population is assumed to be log-normal. The model was validated against experimental data in a specially designed system, where the photorelease of ADP was caused by localized laser stimulus. In this system, a concentration of ADP obeys 2-dimensional Gaussian distribution which broadens due to the diffusion. The response of platelets to the point-like source of ADP is successfully described by the presented model. Our results advance the understanding of platelet function during hemostatic response. The simulation approach can be incorporated into larger computational models of thrombus formation.
导致出血或血栓形成的止血障碍是世界上主要的死亡原因。血小板是止血的主要参与者，对血管壁损伤做出快速的激活反应。在这种情况下，它们会迅速对暴露的化学物质（如 ADP、胶原蛋白和凝血酶）做出反应，切换到激活状态。血小板激活的分子机制是已知的，并且有详细的计算模型可用。然而，对于需要更简单模型的大规模问题（例如血栓生长的模拟）来说，这些模型过于复杂，这些模型仍然需要考虑激动剂浓度的变化和血小板的异质性。在本文中，我们提出了一种简单的血小板群体对空间非均匀刺激反应的模型。首先，模拟血小板的计算节点随机放置在空间中。每个血小板都被分配了特定的激动剂阈值，这决定了它在给定时间是否会被激活。在群体中，阈值值的分布假设为对数正态分布。该模型在一个专门设计的系统中进行了验证，在该系统中，ADP 的光释放是由局部激光刺激引起的。在这个系统中，ADP 的浓度遵循二维高斯分布，由于扩散而变宽。所提出的模型成功地描述了血小板对 ADP 点状源的反应。我们的研究结果加深了对止血反应期间血小板功能的理解。这种模拟方法可以被整合到更大的血栓形成计算模型中。
