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Impact of REDV peptide density and its linker structure on the capture, movement, and adhesion of flowing endothelial progenitor cells in microfluidic devices
Biomaterials Advances ( IF 7.9 ) Pub Date : 2021-08-25 , DOI: 10.1016/j.msec.2021.112381
Atsushi Mahara 1 , Kazuki Kitagawa 2 , Akihisa Otaka 1 , Takahiko Nakaoki 3 , Kazuhiko Ishihara 4 , Tetsuji Yamaoka 1
Affiliation  

Ligand-immobilization to stents and vascular grafts is expected to promote endothelialization by capturing flowing endothelial progenitor cells (EPCs). However, the optimized ligand density and linker structure have not been fully elucidated. Here, we report that flowing EPCs were selectively captured by the REDV peptide conjugated with a short linker. The microchannel surface was modified with the REDV peptide via Gly-Gly-Gly (G3), (Gly-Gly-Gly)3 (G9), and diethylene glycol (diEG) linkers, and the moving velocity and captured ratio were evaluated. On the unmodified microchannels, the moving velocity of the cells exhibited a unimodal distribution similar to the liquid flow. The velocity of the endothelial cells and EPCs on the peptide-immobilized surface indicated a bimodal distribution, and approximately 20 to 30% of cells moved slower than the liquid flow, suggesting that the cells were captured and rolled on the surface. When the immobilized ligand density was lower than 1 molecule/nm2, selective cell capture was observed only in REDV with G3 and diEG linkers, but not in G9 linkers. An in silico study revealed that the G9 linker tends to form a bent structure, and the REDV peptide is oriented to the substrate side. These results indicated that REDV captured the flowing EPC in a sequence-specific manner, and that the short linker was more adequate.



中文翻译:

REDV 肽密度及其接头结构对微流体装置中流动的内皮祖细胞的捕获、运动和粘附的影响

支架和血管移植物的配体固定有望通过捕获流动的内皮祖细胞 (EPC) 来促进内皮化。然而,优化的配体密度和接头结构尚未完全阐明。在这里,我们报告了流动的 EPC 被与短接头缀合的 REDV 肽选择性捕获。微通道表面通过 Gly-Gly-Gly (G3)、(Gly-Gly-Gly) 3用 REDV 肽修饰(G9) 和二甘醇 (diEG) 连接器,以及移动速度和捕获率进行了评估。在未修改的微通道上,细胞的移动速度表现出类似于液体流动的单峰分布。内皮细胞和内皮细胞在肽固定化表面上的速度表明呈双峰分布,大约 20% 到 30% 的细胞比液体流动慢,表明细胞被捕获并在表面滚动。当固定化配体密度低于1分子/nm 2,仅在具有 G3 和 diEG 接头的 REDV 中观察到选择性细胞捕获,但在 G9 接头中未观察到。一项计算机研究表明,G9 接头倾向于形成弯曲结构,而 REDV 肽则朝向底物侧。这些结果表明,REDV 以特定于序列的方式捕获了流动的 EPC,并且短接头更合适。

更新日期:2021-08-30
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