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双路径模型预测的跳跃-斜坡力 regime 下生物捕获键的独特特征。

Distinctive features of the biological catch bond in the jump-ramp force regime predicted by the two-pathway model.

作者信息

Pereverzev Yuriy V, Prezhdo Oleg V, Thomas Wendy E, Sokurenko Evgeni V

机构信息

Department of Chemistry, University of Washington, Seattle, 98195, USA.

出版信息

Phys Rev E Stat Nonlin Soft Matter Phys. 2005 Jul;72(1 Pt 1):010903. doi: 10.1103/PhysRevE.72.010903. Epub 2005 Jul 19.

DOI:10.1103/PhysRevE.72.010903
PMID:16089930
Abstract

The receptor-ligand unbinding in the biological catch bond is analyzed within a simple model that comprises a single bound state and two unbinding pathways. This model is investigated in detail for the jump-ramp force regime, where the pulling force quickly jumps to a finite value and then is ramped linearly with time. Two qualitative criteria are identified that distinguish the catch bond from the slip bond. First, the rupture force probability density of the catch-bond exhibits a maximum-minimum pair, which develops at finite forces. In contrast, the slip bond produces a maximum that first appears at zero force. Second, the catch bond can be identified over a wide range of ramp rates by high rupture probabilities at low forces relative to the probability at the maximum, in contrast to the slip bond, where the probability at the maximum always corresponds to the most likely rupture force. Both distinctive features of the catch bond are masked by large jump forces, indicating that the catch bond is best identified in experiments with moderate loading rates and small jump forces. The catch-bond lifetime in the constant force regime is related to the probability density in the jump-ramp regime, allowing one to determine the bond lifetime for a constant force by measuring the initial probability density in the jump-ramp experiments with different jump forces and a fixed ramp rate. The key analytic results are illustrated with the P -selectin/P-selectin glucoprotein ligand-1 bond.

摘要

在一个包含单一结合态和两条解离途径的简单模型中,分析了生物捕获键中的受体 - 配体解离情况。针对跳变 - 斜坡力模式对该模型进行了详细研究,在这种模式下,拉力迅速跃升至一个有限值,然后随时间线性增加。确定了两个定性标准来区分捕获键和滑动键。首先,捕获键的断裂力概率密度呈现出一个最大值 - 最小值对,它在有限力时出现。相比之下,滑动键产生的最大值首先出现在零力处。其次,与滑动键不同,捕获键在较宽的斜坡速率范围内,相对于最大值处的概率,在低力时具有较高的断裂概率,而在滑动键中,最大值处的概率总是对应最可能的断裂力。捕获键的这两个独特特征会被较大的跳变力掩盖,这表明在中等加载速率和小跳变力的实验中最容易识别捕获键。恒力模式下捕获键的寿命与跳变 - 斜坡模式下的概率密度相关,这使得人们可以通过测量不同跳变力和固定斜坡速率的跳变 - 斜坡实验中的初始概率密度来确定恒力下的键寿命。关键的分析结果通过P - 选择素/P - 选择素糖蛋白配体 -1键进行了说明。

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