Self-assembly and bioactivity of a polymer/peptide conjugate containing the RGD cell adhesion motif and PEG

Self-assembly and bioactivity of a polymer/peptide conjugate containing the RGD cell adhesion motif and PEG
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DOI:
10.1016/j.eurpolymj.2013.02.016
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发表时间:
2013-10-01
影响因子:
6
通讯作者:
Hamley, Ian W.
Hamley, Ian W.
中科院分区:
化学2区
文献类型:
--
作者:
Castelletto, Valeria;Gouveia, Ricardo J.;Hamley, Ian W.

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研究了含有RGD细胞黏附基序的多肽-聚合物偶联物DGRFFF-PEG3000在水溶液中的自组装和生物活性。通过引入三个疏水的苯丙氨酸残基以及RGD单元和摩尔质量为3000 kg摩尔(-1)的短链聚乙二醇链,该偶联物被设计为两亲性的。在由荧光测量确定的临界聚集浓度以上,通过光谱测量和X射线衍射揭示了p-Sheet结构的信号。在高浓度下,电子显微镜观察到了自组装的纤维纳米结构。尽管干燥时会发生聚乙二醇结晶,但仍能观察到原纤维。这表明DGRFFF具有足够强的聚集倾向,不会被聚乙二醇结晶所阻止。对人角膜成纤维细胞在组织培养板(TCPs)和低附着平板上的粘附性、存活率和增殖率进行了检测。在磷酸三钙上,以足够低的浓度制备的DGRFFF-PEG3000薄膜是可行的,并观察到了细胞的增殖;而在低附着表面,既没有观察到细胞的黏附,也没有观察到细胞的增殖,这表明RGD基序不能增强细胞的黏附。这归因于自组装纤维的核-壳结构,其多肽核心被聚乙二醇壳包围,这阻碍了对RGD单元的访问。(C)2013爱思唯尔有限公司。保留所有权利。
The self-assembly and bioactivity of the peptide-polymer conjugate DGRFFF-PEG3000 containing the RGD cell adhesion motif has been examined, in aqueous solution. The conjugate is designed to be amphiphilic by incorporation of three hydrophobic phenylalanine residues as well as the RGD unit and a short poly(ethylene glycol) (PEG) chain of molar mass 3000 kg mol(-1). Above a critical aggregation concentration, determined by fluorescence measurements, signals of p-sheet structure are revealed by spectroscopic measurements, as well as X-ray diffraction. At high concentration, a self-assembled fibril nanostructure is revealed by electron microscopy. The fibrils are observed despite PEG crystallization which occurs on drying. This suggests that DGRFFF has an aggregation tendency that is sufficiently strong not to be prevented by PEG crystallization. The adhesion, viability and proliferation of human corneal fibroblasts was examined for films of the conjugate on tissue culture plates (TCPs) as well as low attachment plates. On TCP, DGRFFF-PEG3000 films prepared at sufficiently low concentration are viable, and cell proliferation is observed: However, on low attachment surfaces, neither cell adhesion nor proliferation was observed, indicating that the RGD motif was not available to enhance cell adhesion. This was ascribed to the core-shell architecture of the self-assembled fibrils with a peptide core surrounded by a PEG shell which hinders access to the RGD unit. (C) 2013 Elsevier Ltd. All rights reserved.