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脑微血管内皮细胞在微图案水凝胶上的取向受葡萄糖水平变化的影响。

Brain microvasculature endothelial cell orientation on micropatterned hydrogels is affected by glucose level variations.

机构信息

Department of Materials Science and Engineering, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Department of Biomedical Engineering, Lund University, Lund, Sweden.

出版信息

Sci Rep. 2021 Oct 4;11(1):19608. doi: 10.1038/s41598-021-99136-9.

Abstract

This work reports on an effort to decipher the alignment of brain microvasculature endothelial cells to physical constrains generated via adhesion control on hydrogel surfaces and explore the corresponding responses upon glucose level variations emulating the hypo- and hyperglycaemic effects in diabetes. We prepared hydrogels of hyaluronic acid a natural biomaterial that does not naturally support endothelial cell adhesion, and specifically functionalised RGD peptides into lines using UV-mediated linkage. The width of the lines was varied from 10 to 100 µm. We evaluated cell alignment by measuring the nuclei, cell, and F-actin orientations, and the nuclei and cell eccentricity via immunofluorescent staining and image analysis. We found that the brain microvascular endothelial cells aligned and elongated to these physical constraints for all line widths. In addition, we also observed that varying the cell medium glucose levels affected the cell alignment along the patterns. We believe our results may provide a platform for further studies on the impact of altered glucose levels in cardiovascular disease.

摘要

本工作旨在破译大脑微血管内皮细胞在水凝胶表面的黏附控制所产生的物理约束下的排列方式,并探索在模拟糖尿病低血糖和高血糖效应的葡萄糖水平变化下的相应反应。我们制备了透明质酸水凝胶——一种天然生物材料,其本身并不支持内皮细胞黏附,并通过紫外光介导的键合将 RGD 肽特异性地功能化为线。线的宽度从 10 到 100 μm 不等。我们通过测量细胞核、细胞和 F-肌动蛋白的取向以及通过免疫荧光染色和图像分析测量细胞核和细胞的偏心率来评估细胞的取向。我们发现,大脑微血管内皮细胞在所有线宽下都能对线状结构进行排列和延伸。此外,我们还观察到,改变细胞培养基中的葡萄糖水平会影响细胞沿图案的排列。我们相信,我们的研究结果可能为进一步研究葡萄糖水平改变对心血管疾病的影响提供一个平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97d3/8490407/58b6ae7d1182/41598_2021_99136_Fig1_HTML.jpg

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