Biomimetic channel modeling local vascular dynamics of pro-inflammatory endothelial changes.
Biomimetic channel modeling local vascular dynamics of pro-inflammatory endothelial changes.
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DOI：
10.1063/1.4936672
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发表时间：
2016-01
期刊：
影响因子：
3.2
通讯作者：
Antony Thomas;H. Daniel Ou-Yang;L. Lowe-Krentz;V. Muzykantov;Yaling Liu
中科院分区：
文献类型：
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作者：
Antony Thomas;H. Daniel Ou-Yang;L. Lowe-Krentz;V. Muzykantov;Yaling Liu
内皮细胞构成血管的内皮层，并暴露于各种因素之下，如血液动力学条件（剪切应力、层流和湍流）、生化信号（细胞因子）以及与其他细胞类型（平滑肌细胞、单核细胞、血小板等）的交流。血管功能受这些因素之间的相互作用所调节。病理状况的出现会导致血管内皮衬里上细胞黏附分子的局部上调。这一过程由循环细胞因子如肿瘤坏死因子 -α所促进，它会导致细胞间黏附分子 -1（ICAM -1）等分子在内皮细胞表面表达。ICAM -1在调节内皮细胞层的动态完整性和细胞骨架重塑方面至关重要，并且作为炎症反应和伤口愈合的一部分介导直接的细胞 - 细胞相互作用。在这项研究中，我们通过在微流控平台上培养融合的、流动排列的内皮细胞，开发了一种仿生血管模型，并对流动介导的局部促炎内皮激活进行了实时原位表征。该模型模拟了从组织侧细胞因子激活内皮的生理现象，并研究了局部表面ICAM -1表达和F - 肌动蛋白排列的异质性。荧光抗体包被的颗粒被用作识别内皮细胞表面ICAM -1表达的成像探针。在流动条件下，针对两种不同的颗粒大小和抗体包被密度评估了颗粒的结合特性。这使得能够研究内皮细胞上表达的ICAM -1分子的空间分辨率和可及性，以及它们在受体 - 配体识别和结合方面的敏感性。这项工作开发了一种体外血管模型，该模型能够整合各种异质性因素以有效模拟复杂的内皮微环境，并有可能应用于相关的血管力学生物学研究。
Endothelial cells form the inner lining of blood vessels and are exposed to various factors like hemodynamic conditions (shear stress, laminar, and turbulent flow), biochemical signals (cytokines), and communication with other cell types (smooth muscle cells, monocytes, platelets, etc.). Blood vessel functions are regulated by interactions among these factors. The occurrence of a pathological condition would lead to localized upregulation of cell adhesion molecules on the endothelial lining of the blood vessel. This process is promoted by circulating cytokines such as tumor necrosis factor-alpha, which leads to expression of intercellular adhesion molecule-1 (ICAM-1) on the endothelial cell surface among other molecules. ICAM-1 is critical in regulating endothelial cell layer dynamic integrity and cytoskeletal remodeling and also mediates direct cell-cell interactions as part of inflammatory responses and wound healing. In this study, we developed a biomimetic blood vessel model by culturing confluent, flow aligned, endothelial cells in a microfluidic platform, and performed real time in situ characterization of flow mediated localized pro-inflammatory endothelial activation. The model mimics the physiological phenomenon of cytokine activation of endothelium from the tissue side and studies the heterogeneity in localized surface ICAM-1 expression and F-actin arrangement. Fluorescent antibody coated particles were used as imaging probes for identifying endothelial cell surface ICAM-1 expression. The binding properties of particles were evaluated under flow for two different particle sizes and antibody coating densities. This allowed the investigation of spatial resolution and accessibility of ICAM-1 molecules expressed on the endothelial cells, along with their sensitivity in receptor-ligand recognition and binding. This work has developed an in vitro blood vessel model that can integrate various heterogeneous factors to effectively mimic a complex endothelial microenvironment and can be potentially applied for relevant blood vessel mechanobiology studies.