Photodynamic control of bioactivity in a nanofiber matrix.

Photodynamic control of bioactivity in a nanofiber matrix.
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DOI:
10.1021/nn304101x
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发表时间:
2012-12-21
期刊:
影响因子:
17.1
通讯作者:
Stupp, Samuel I.
Stupp, Samuel I.
中科院分区:
材料科学1区
文献类型:
--
作者:
Sur, Shantanu;Matson, John B.;Webber, Matthew J.;Newcomb, Christina J.;Stupp, Samuel I.

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自组装肽材料通过在合成基质上呈递生物活性表位而被广泛用于模拟天然细胞外基质(ECM)。虽然这种方法可以促进来自在基质中生长的细胞的期望的响应,但是它缺乏对所呈现的信号进行空间或时间调节的能力。我们在这里描述了一个光响应,合成ECM使用超分子平台组成的肽两亲物(PA),自组装成圆柱形纳米纤维。使用与微波辅助固相肽合成相容的新型Fmoc-氨基酸,将可光裂解的硝基苄基酯基团包括在肽骨架中。在肽骨架上放置光不稳定基团使得能够在暴露于光时从PA分子中有效去除ECM衍生的细胞粘附表位RGDS(光解半衰期约1.9分钟),而不影响ECM组装。通过免疫染色和细胞形态学分析确定,与未功能化和对照(RGES呈递)表面相比,RGDS呈递PA基质上培养的成纤维细胞表现出细胞扩散增加和更成熟的粘着斑。此外,当培养物暴露于光时,我们观察到成纤维细胞在含有可裂解RGDS表位的基质上扩散的停滞;相反,当RGDS表位通过光不敏感的对照接头连接到PA分子时,细胞应答的这种动态变化不存在。光响应生物活性材料可以有助于更接近地模拟天然ECM的动态性质的合成系统的开发。
Self-assembling peptide materials have been used extensively to mimic natural extracellular matrices (ECMs) by presenting bioactive epitopes on a synthetic matrix. Although this approach can facilitate a desired response from cells grown in the matrix, it lacks the capacity for spatial or temporal regulation of the presented signals. We describe here a photo-responsive, synthetic ECM using a supramolecular platform comprised of peptide amphiphiles (PAs) that self-assemble into cylindrical nanofibers. A photocleavable nitrobenzyl ester group was included in the peptide backbone using a novel Fmoc-amino acid that is compatible with microwave-assisted solid phase peptide synthesis. The placement of the photolabile group on the peptide backbone enabled efficient removal of the ECM-derived cell adhesion epitope RGDS from PA molecules upon exposure to light (half-life of photolysis ~ 1.9 min) without affecting the nanofiber assembly. Fibroblasts cultured on RGDS-presenting PA nanofiber substrates demonstrated increased cell spreading and more mature focal adhesions compared with unfunctionalized and control (RGES-presenting) surfaces, as determined by immunostaining and cell morphological analysis. Furthermore, we observed an arrest in fibroblast spreading on substrates containing a cleavable RGDS epitope when the culture was exposed to light; in contrast, this dynamic shift in cell response was absent when the RGDS epitope was attached to the PA molecule by a light-insensitive control linker. Light-responsive bioactive materials can contribute to the development of synthetic systems that more closely mimic the dynamic nature of native ECM.
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