Multiscale model of platelet translocation and collision.

Multiscale model of platelet translocation and collision.
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血小板易位和碰撞的多尺度模型。

DOI:
10.1016/j.jcp.2012.08.014
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发表时间:
2013
影响因子:
4.1
通讯作者:
King,MichaelR
King,MichaelR
中科院分区:
物理与天体物理2区
文献类型:
--
作者:
Wang,Weiwei;Mody,NipaA;King,MichaelR

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由糖蛋白ibb α (GPIbα) -血管性血液病因子(vWF)键介导的血小板在受损血管表面的拴系,以及流动血小板和粘附血小板之间的相互作用,是血管损伤后立即发生的两个关键事件。这种早期血小板沉积和积聚触发了止血的开始,这是一种自我防御机制,以防止身体失血过多。为了理解和预测这一复杂的过程,人们必须在非常小的时间框架(1-1000μs)和长度尺度(10-100nm)内整合实验确定的参与受体的力学和生化动力学信息,以发生在几秒钟和几十微米内的集体现象。在本研究中,一个独特的三维多尺度计算模型,血小板粘附动力学(PAD),被用于阐明(i)一个非球形的圆盘形血小板相互作用和系在受损血管壁上,然后(ii)流动血小板与下游粘附血小板之间的碰撞相互作用的独特物理。通过分析不同生理条件下的大量模拟,我们得出结论,血小板独特的球形提供了异质的、取向依赖的易位(滚动)行为,增强了细胞壁的相互作用。我们还得出结论,血小板-血小板近场相互作用对微血栓形成过程中细胞间的通讯至关重要。这里描述的PAD模型有助于确定在此过程中控制血小板捕获初始阶段的物理因素。
The tethering of platelets on the injured vessel surface mediated by glycoprotein Ibα (GPIbα) – Von Willebrand factor (vWF) bonds, as well as the interaction between flowing platelets and adherent platelets, are two key events that take place immediately following blood vessel injury. This early-stage platelet deposition and accumulation triggers the initiation of hemostasis, a self-defensive mechanism to prevent the body from excessive blood loss. To understand and predict this complex process, one must integrate experimentally determined information on the mechanics and biochemical kinetics of participating receptors over very small time frames (1–1000μs) and length scales (10–100nm), to collective phenomena occurring over seconds and tens of microns. In the present study, a unique three dimensional multiscale computational model, Platelet Adhesive Dynamics (PAD), was applied to elucidate the unique physics of (i) a non-spherical, disk-shaped platelet interacting and tethering onto the damaged vessel wall followed by (ii) collisional interactions between a flowing platelet with a downstream adherent platelet. By analyzing numerous simulations under different physiological conditions, we conclude that the platelet’s unique spheroid-shape provides heterogeneous, orientation-dependent translocation (rolling) behavior which enhances cell-wall interactions. We also conclude that platelet–platelet near field interactions are critical for cell–cell communication during the initiation of microthrombi. The PAD model described here helps to identify the physical factors that control the initial stages of platelet capture during this process.
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