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剪切流中基于黏附键的细胞黏附的力学模型。

Mechanical Model for Catch-Bond-Mediated Cell Adhesion in Shear Flow.

机构信息

Key Laboratory of Mechanics on Disaster and Environment in Western China, Ministry of Education, College of Civil Engineering and Mechanics, Lanzhou University, Lanzhou 730000, China.

PULS Group, Institute for Theoretical Physics, FAU Erlangen-Nürnberg, 91058 Erlangen, Germany.

出版信息

Int J Mol Sci. 2020 Jan 16;21(2):584. doi: 10.3390/ijms21020584.

DOI:10.3390/ijms21020584
PMID:31963253
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7013535/
Abstract

Catch bond, whose lifetime increases with applied tensile force, can often mediate rolling adhesion of cells in a hydrodynamic environment. However, the mechanical mechanism governing the kinetics of rolling adhesion of cells through catch-bond under shear flow is not yet clear. In this study, a mechanical model is proposed for catch-bond-mediated cell adhesion in shear flow. The stochastic reaction of bond formation and dissociation is described as a Markovian process, whereas the dynamic motion of cells follows classical analytical mechanics. The steady state of cells significantly depends on the shear rate of flow. The upper and lower critical shear rates required for cell detachment and attachment are extracted, respectively. When the shear rate increases from the lower threshold to the upper threshold, cell rolling became slower and more regular, implying the flow-enhanced adhesion phenomenon. Our results suggest that this flow-enhanced stability of rolling adhesion is attributed to the competition between stochastic reactions of bonds and dynamics of cell rolling, instead of force lengthening the lifetime of catch bonds, thereby challenging the current view in understanding the mechanism behind this flow-enhanced adhesion phenomenon. Moreover, the loading history of flow defining bistability of cell adhesion in shear flow is predicted. These theoretical predictions are verified by Monte Carlo simulations and are related to the experimental observations reported in literature.

摘要

牵张激活键(catch bond)的寿命随所施加的张力而增加,通常可以介导细胞在流体动力学环境中的滚动黏附。然而,通过剪切流中的牵张激活键来控制细胞滚动黏附动力学的力学机制尚不清楚。在本研究中,提出了一个用于剪切流中牵张激活键介导的细胞黏附的力学模型。键的形成和解离的随机反应被描述为马尔可夫过程,而细胞的动态运动则遵循经典分析力学。细胞的稳态显著取决于流动的剪切率。分别提取了用于细胞脱离和附着的上下临界剪切率。当剪切率从低阈值增加到高阈值时,细胞滚动变得更慢且更规则,表明存在流动增强黏附现象。我们的结果表明,这种流动增强的滚动黏附稳定性归因于键的随机反应和细胞滚动动力学之间的竞争,而不是力延长了牵张激活键的寿命,从而挑战了当前对这种流动增强黏附现象背后机制的理解。此外,还预测了流动定义剪切流中细胞黏附双稳定性的加载历史。这些理论预测通过蒙特卡罗模拟得到验证,并与文献中报道的实验观察结果相关。

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