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血小板激活过程中形状及其演变的模拟方法。

Method for the simulation of blood platelet shape and its evolution during activation.

机构信息

Novosibirsk State University, Novosibirsk, Russia.

Voevodsky Institute of Chemical Kinetics and Combustion SB RAS, Novosibirsk, Russia.

出版信息

PLoS Comput Biol. 2018 Mar 8;14(3):e1005899. doi: 10.1371/journal.pcbi.1005899. eCollection 2018 Mar.

Abstract

We present a simple physically based quantitative model of blood platelet shape and its evolution during agonist-induced activation. The model is based on the consideration of two major cytoskeletal elements: the marginal band of microtubules and the submembrane cortex. Mathematically, we consider the problem of minimization of surface area constrained to confine the marginal band and a certain cellular volume. For resting platelets, the marginal band appears as a peripheral ring, allowing for the analytical solution of the minimization problem. Upon activation, the marginal band coils out of plane and forms 3D convoluted structure. We show that its shape is well approximated by an overcurved circle, a mathematical concept of closed curve with constant excessive curvature. Possible mechanisms leading to such marginal band coiling are discussed, resulting in simple parametric expression for the marginal band shape during platelet activation. The excessive curvature of marginal band is a convenient state variable which tracks the progress of activation. The cell surface is determined using numerical optimization. The shapes are strictly mathematically defined by only three parameters and show good agreement with literature data. They can be utilized in simulation of platelets interaction with different physical fields, e.g. for the description of hydrodynamic and mechanical properties of platelets, leading to better understanding of platelets margination and adhesion and thrombus formation in blood flow. It would also facilitate precise characterization of platelets in clinical diagnosis, where a novel optical model is needed for the correct solution of inverse light-scattering problem.

摘要

我们提出了一种简单的基于物理的血小板形状及其在激动剂诱导激活过程中演变的定量模型。该模型基于对两个主要细胞骨架元素的考虑:微管的边缘带和亚膜皮质。从数学上考虑,我们考虑了在限制边缘带和一定细胞体积的情况下最小化表面积的问题。对于静止的血小板,边缘带呈现为外围环,允许对最小化问题进行解析解。在激活时,边缘带从平面卷曲并形成 3D 卷曲结构。我们表明,其形状可以很好地由过弯曲圆近似,这是具有恒定过曲率的封闭曲线的数学概念。讨论了导致这种边缘带卷曲的可能机制,从而得到了血小板激活过程中边缘带形状的简单参数表达式。边缘带的过曲率是一个方便的状态变量,可跟踪激活的进展。使用数值优化确定细胞表面。这些形状仅由三个参数严格数学定义,并与文献数据吻合良好。它们可用于模拟血小板与不同物理场的相互作用,例如描述血小板的流体动力学和力学特性,从而更好地理解血小板在血流中的靠边和粘附以及血栓形成。它还将有助于在临床诊断中对血小板进行精确表征,其中需要一种新的光学模型来正确解决反向光散射问题。

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