Application of multiple levels of fluid shear stress to endothelial cells plated on polyacrylamide gels.
Application of multiple levels of fluid shear stress to endothelial cells plated on polyacrylamide gels.
复制标题
将多个水平的流体剪应力应用于聚丙烯酰胺凝胶上的内皮细胞。
DOI：
10.1039/c4lc01236d
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发表时间：
2015-02-21
期刊：
影响因子：
6.1
通讯作者：
Janmey PA
中科院分区：
文献类型：
--
作者：
Galie PA;van Oosten A;Chen CS;Janmey PA
内皮细胞对流体剪切应力反应的测量先前已在非生态性刚性基质上进行。我们描述了一种微流体装置的设计和实现，该装置可将离散水平的剪切应力应用于涂在具有生理相关刚度的水凝胶基基底上的细胞。该装置允许测量细胞形态和对联合刺激的炎症反应，并确定血管硬化导致血流病理反应的机制。我们发现，影响内皮细胞形态和炎症反应所需的剪切应力的大小取决于基质刚度。与对照组相比，100 Pa底物处理的内皮细胞对TNF-α处理的细胞面积和皮质硬度增加更大，NF-κB核易位减少。软基质内皮细胞对剪切应力的反应取决于透明质酸（HA）的存在。这些结果强调了底物硬度对内皮功能的重要性，并阐明了衰老和疾病中血管硬化对内皮的影响。
Measurements of endothelial cell response to fluid shear stress have previously been performed on unphysiologically rigid substrates. We describe the design and implementation of a microfluidic device that applies discrete levels of shear stress to cells plated on hydrogel-based substrates of physiologicallyrelevant stiffness. The setup allows for measurements of cell morphology and inflammatory response to the combined stimuli, and identifies mechanisms by which vascular stiffening leads to pathological responses to blood flow. We found that the magnitude of shear stress required to affect endothelial cell morphology and inflammatory response depended on substrate stiffness. Endothelial cells on 100 Pa substrates demonstrate a greater increase in cell area and cortical stiffness and decrease in NF-κB nuclear translocation in response to TNF-α treatment compared to controls than cells plated on 10 kPa substrates. The response of endothelial cells on soft substrates to shear stress depends on the presence of hyaluronan (HA). These results emphasize the importance of substrate stiffness on endothelial function, and elucidate a means by which vascular stiffening in aging and disease can impact the endothelium.