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在模型肺毛细血管网络中单核细胞的机械适应性。

Mechanical adaptation of monocytes in model lung capillary networks.

机构信息

Laboratoire Adhesion et Inflammation, Aix Marseille University, CNRS, INSERM, 13009 Marseille, France.

Centre Interdisciplinaire de Nanoscience de Marseille, Aix Marseille University, CNRS, 13009 Marseille, France.

出版信息

Proc Natl Acad Sci U S A. 2020 Jun 30;117(26):14798-14804. doi: 10.1073/pnas.1919984117. Epub 2020 Jun 17.

Abstract

Proper circulation of white blood cells (WBCs) in the pulmonary vascular bed is crucial for an effective immune response. In this branched vascular network, WBCs have to strongly deform to pass through the narrowest capillaries and bifurcations. Although it is known that this process depends on the cell mechanical properties, it is still poorly understood due to the lack of a comprehensive model of cell mechanics and of physiologically relevant experiments. Here, using an in-house microfluidic device mimicking the pulmonary capillary bed, we show that the dynamics of THP1 monocytes evolves along successive capillary-like channels, from a nonstationary slow motion with hops to a fast and smooth efficient one. We used actin cytoskeleton drugs to modify the traffic dynamics. This led us to propose a simple mechanical model that shows that a very finely tuned cortical tension combined with a high cell viscosity governs the fast transit through the network while preserving cell integrity. We finally highlight that the cortical tension controls the steady-state cell velocity via the viscous friction between the cell and the channel walls.

摘要

白细胞(WBC)在肺部血管床中的正常循环对于有效的免疫反应至关重要。在这个分支的血管网络中,WBC 必须强烈变形才能通过最窄的毛细血管和分支。尽管已知这个过程取决于细胞的机械特性,但由于缺乏细胞力学的综合模型和与生理相关的实验,因此仍然知之甚少。在这里,我们使用一种内部微流控装置模拟肺部毛细血管床,结果表明,THP1 单核细胞的动力学沿着连续的毛细血管样通道演变,从具有跳跃的非稳态缓慢运动到快速和顺畅的有效运动。我们使用肌动蛋白细胞骨架药物来改变交通动力学。这使我们提出了一个简单的力学模型,表明非常精细调节的皮质张力与高细胞粘度相结合,控制着细胞在网络中的快速传输,同时保持细胞完整性。最后,我们强调皮质张力通过细胞与通道壁之间的粘性摩擦力控制稳态细胞速度。

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本文引用的文献

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A comparison of methods to assess cell mechanical properties.细胞力学特性评估方法的比较。
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