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Switching behaviour in vascular smooth muscle cell-matrix adhesion during oscillatory loading.
Journal of Theoretical Biology ( IF 2 ) Pub Date : 2020-06-27 , DOI: 10.1016/j.jtbi.2020.110387
Linda Irons 1 , Huang Huang 2 , Markus R Owen 1 , Reuben D O'Dea 1 , Gerald A Meininger 2 , Bindi S Brook 1
Affiliation  

Integrins regulate mechanotransduction between smooth muscle cells (SMCs) and the extracellular matrix (ECM). SMCs resident in the walls of airways or blood vessels are continuously exposed to dynamic mechanical forces due to breathing or pulsatile blood flow. However, the resulting effects of these forces on integrin dynamics and associated cell–matrix adhesion are not well understood. Here we present experimental results from atomic force microscopy (AFM) experiments, designed to study the integrin response to external oscillatory loading of varying amplitudes applied to live aortic SMCs, together with theoretical results from a mathematical model. In the AFM experiments, a fibronectin-coated probe was used cyclically to indent and retract from the surface of the cell. We observed a transition between states of firm adhesion and of complete detachment as the amplitude of oscillatory loading increased, revealed by qualitative changes in the force timecourses. Interestingly, for some of the SMCs in the experiments, switching behaviour between the two adhesion states is observed during single timecourses at intermediate amplitudes. We obtain two qualitatively similar adhesion states in the mathematical model, where we simulate the cell, integrins and ECM as an evolving system of springs, incorporating local integrin binding dynamics. In the mathematical model, we observe a region of bistability where both the firm adhesion and detachment states can occur depending on the initial adhesion state. The differences are seen to be a result of mechanical cooperativity of integrins and cell deformation. Switching behaviour is a phenomenon associated with bistability in a stochastic system, and bistability in our deterministic mathematical model provides a potential physical explanation for the experimental results. Physiologically, bistability provides a means for transient mechanical stimuli to induce long-term changes in adhesion dynamics—and thereby the cells’ ability to transmit force—and we propose further experiments for testing this hypothesis.



中文翻译:

振荡加载过程中血管平滑肌细胞-基质粘附的转换行为。

整合素调节平滑肌细胞 (SMC) 和细胞外基质 (ECM) 之间的机械转导。由于呼吸或脉动血流,驻留在气道或血管壁中的 SMC 不断受到动态机械力的影响。然而,这些力对整合素动力学和相关细胞 - 基质粘附的影响尚不清楚。在这里,我们展示了原子力显微镜 (AFM) 实验的实验结果,旨在研究整合素对应用于活主动脉 SMC 的不同振幅的外部振荡载荷的响应,以及数学模型的理论结果。在 AFM 实验中,纤维连接蛋白包被的探针被循环使用以从细胞表面缩进和缩回。我们观察到随着振荡载荷幅度的增加,牢固粘附状态和完全脱离状态之间的转变,通过力时间过程的质变来揭示。有趣的是,对于实验中的一些 SMC,在中间幅度的单个时间过程中观察到两种粘附状态之间的切换行为。我们在数学模型中获得了两种性质相似的粘附状态,其中我们将细胞、整合素和 ECM 模拟为一个不断发展的弹簧系统,并结合了局部整合素结合动力学。在数学模型中,我们观察到一个双稳态区域,根据初始粘附状态,在该区域可以发生牢固的粘附和分离状态。差异被认为是整合素和细胞变形的机械协同作用的结果。开关行为是随机系统中与双稳态相关的现象,我们确定性数学模型中的双稳态为实验结果提供了潜在的物理解释。在生理学上,双稳态为瞬时机械刺激提供了一种手段,以诱导粘附动力学的长期变化——从而诱导细胞传递力的能力——我们建议进一步的实验来测试这一假设。

更新日期:2020-07-03
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