The effect of extensible PEG tethers on shielding between grafted thermo-responsive polymer chains and integrin-RGD binding
The effect of extensible PEG tethers on shielding between grafted thermo-responsive polymer chains and integrin-RGD binding
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DOI：
10.1016/j.biomaterials.2008.05.030
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发表时间：
2008-09-01
期刊：
影响因子：
14
通讯作者：
Okano, Teruo
中科院分区：
文献类型：
--
作者：
Ebara, Mitsuhiro;Yamato, Masayuki;Okano, Teruo
整合素-RGD（Arg-Gly-Asp）结合的热“开-关”开关的亲和力控制已实现使用新设计的表面呈现接枝的温度响应性聚（N-异丙基丙烯酰胺-co-2-羧基异丙基丙烯酰胺）共聚物与合成肽功能化。所制备的表面被设计成暴露可用于在高于下临界溶液温度（LCST）的活性“开”状态下细胞结合的拴系肽。另一方面，完全延伸的链完全掩蔽肽，并且细胞在低于LCST的非活性“关闭”状态下开始从表面脱离。本文阐述了屏蔽效应的接枝聚合物链的解离整合素-RGD结合低于LCST。为了评估聚合物屏蔽的能力，在肽和接枝聚合物之间引入可延伸的聚（乙二醇）（PEG）系链。PEG链允许肽通过功能性PEG端基栓系到表面，导致甚至低于LCST的活性“开”状态。当肽与可延伸的系链末端偶联时，发现从表面释放细胞所需的时间更长，这表明表面可以通过共价结合到PEG链的游离末端的粘合剂部分产生细胞附着。这些结果表明，在纳米长度尺度上的结构变化是至关重要的控制整合素-RGD的结合和导致细胞脱离的主要因素之一是接枝聚合物链的屏蔽效应。(C)2008爱思唯尔有限公司保留所有权利。
The affinity control of integrin-RGD (Arg-Gly-Asp) binding by a thermal "on-off' switch has been achieved using newly designed surfaces presenting grafted temperature-responsive poly(N-isopropylacrylamide-co-2-carboxyisopropylacrylamide) copolymers functionalized with synthetic peptides. The prepared surface was designed to expose the tethered peptides available for cell binding at active "on" state above the lower critical solution temperature (LCST). The fully extended chains, on the other hand, masked the peptides completely and the cells started to detach from the surfaces at inactive "off' sate below the LCST. This paper elucidates the shielding effect of the grafted polymer chains on the dissociation of integrin-RGD binding below the LCST. To assess the ability of the polymer-shielding, extensible poly(ethylene glycol) (PEG) tethers were introduced between peptides and the grafted polymers. PEG chains allow peptides to be tethered to surfaces via functional PEG end-groups, leading to active "on" state even below the LCST. The time required to release cells from the surface was found to be longer when peptides were coupled to an extensible tether ends, suggesting that the surfaces can engender cell attachment through adhesive moieties covalently bound to the free ends of PEG chains. These results indicate that architectural changes on the nanometer length scale are crucial for controlling integrin-RGD binding and one of the main factors causing cell detachment is the shielding effect of the grafted polymer chains. (C) 2008 Elsevier Ltd. All rights reserved.