Poly(ethylene glycol) as a sensitive regulator of cell survival fate on polymeric biomaterials: the interplay of cell adhesion and pro-oxidant signaling mechanisms
Poly(ethylene glycol) as a sensitive regulator of cell survival fate on polymeric biomaterials: the interplay of cell adhesion and pro-oxidant signaling mechanisms
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DOI：
10.1039/c0sm00172d
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发表时间：
2010-01-01
期刊：
影响因子：
3.4
通讯作者：
Kohn, Joachim
中科院分区：
文献类型：
--
作者：
Sung, Hak-Joon;Luk, Arnold;Kohn, Joachim
聚乙二醇(PEG)是一种广泛应用于多种平台的化合物，在医疗领域的应用日益广泛。用含有不同摩尔百分比聚乙二醇酯(M-w1000)的聚碳酸酯研究聚乙二醇酯对细胞黏附、增殖、铺展和存活的影响。两个截然不同的聚乙二醇介导的细胞信号元件影响这些细胞行为：(1)整合素α5受体介导的细胞与生物材料表面的焦点黏附；(2)通过产生活性氧(ROS)来调节细胞的氧化还原和细胞凋亡。在较低的聚乙二醇(1k)摩尔%(5%和8%)下，细胞的附着和铺展由于ROS的影响而降低，而在所研究的较高的聚乙二醇(1k)摩尔%(10%和20%)时，观察到了不寻常的超黏附行为。在较高的聚乙二醇(1K)浓度下，细胞铺展能力显著增强，整合素α5受体的免疫定位和整合素α5基因的mRNA表达增强证实了这一点。这些细胞对较高的聚乙二醇(1k)摩尔%共聚物的反应足以克服ROS对caspase激活和细胞收缩的影响，而在较低的聚乙二醇(1k)摩尔%时，这种影响占主导地位。这些研究阐明了聚乙二醇介导的细胞信号转导，这意味着富含聚乙二醇的材料的黏附和凋亡活性可以通过添加抗氧化剂来敏感地控制。此外，这项研究表明，生物材料可以通过同时发生的性质变化来驱动细胞的命运朝着相反的方向发展。
Poly(ethylene glycol) (PEG) is one of the most widely used compounds across a variety of platforms and is increasingly found in medical applications. Polycarbonates containing varying mol% of PEG (M-w 1000) were used to probe the effects of PEG on cell adhesion, proliferation, spreading, and survival. Two contrasting PEG-mediated cell signaling elements affected these cellular behaviors: (i) integrin alpha 5 receptor mediated cellular focal adhesions to the biomaterial surface and (ii) modulation of cellular redox and apoptosis through generation of reactive oxygen species (ROS). At lower PEG(1k) mol% (5% and 8%) cell attachment and spreading decreased concomitantly due to ROS, whereas at the higher PEG(1k) mol% studied (10% and 20%) an unusual super-adhesive behavior was observed. At higher PEG(1k) mol% cells exhibited greatly enhanced spreading, which was confirmed through immunolocalization of integrin alpha 5 receptors and enhanced mRNA expression of the integrin alpha 5 gene. These cellular responses on higher PEG(1k) mol% co-polymers were sufficient to overcome the ROS-driven effects on caspase activation and cell shrinkage, which dominated at lower PEG(1k) mol%. These studies elucidate PEG-mediated cellular signaling with the implication that the adhesion and apoptotic activity of PEG-rich materials can be sensitively controlled by anti-oxidant addition. Moreover, this study shows that biomaterials can drive the cell fate in opposing directions through concurrent property changes.