Dynamic display of bioactivity through host-guest chemistry.

Dynamic display of bioactivity through host-guest chemistry.
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DOI:
10.1002/anie.201306278
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发表时间:
2013-11-11
影响因子:
16.6
通讯作者:
Stupp, Samuel I.
Stupp, Samuel I.
中科院分区:
化学1区
文献类型:
--
作者:
Boekhoven, Job;Perez, Charles M. Rubert;Sur, Shantanu;Worthy, Amanda;Stupp, Samuel I.

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细胞外基质(ECM)不仅在细胞周围形成支撑结构,而且为细胞提供必要的机械和化学线索。这些线索可以指导细胞粘附、迁移、增殖或分化,从而介导组织发育、组织再生和伤口愈合这些生物过程需要分子动态ECM来实现对信号显示的时空控制在过去的几十年里,许多具有生物活性的短肽序列已经被鉴定出来,它们模拟了这些信号。在细胞外蛋白纤维连接蛋白中发现的肽序列RGDS已被广泛研究以开发人工基质。该序列已被发现与跨膜整合素蛋白结合,启动多种蛋白质的募集,从而产生附着于细胞骨架的结构域,称为局灶性粘附局灶黏附的形成允许细胞扩散并激活导致基因表达的各种途径。研究表明,与人工基质共轭的RGDS序列的存在解决了局灶粘连的形成例如,与这种人工基质的附着已被证明可诱导成纤维细胞、人间充质干细胞[6]和人内皮细胞[7]等的粘附和扩散动态显示线索的人工基质将有助于理解生物过程,并使组织再生治疗的发展成为可能。西北大学。edu网站:http://stupp。西北。edu。
The extracellular matrix (ECM) not only forms the supporting structure around cells but also offers them essential mechanical and chemical cues. Such cues can instruct cells to adhere, migrate, proliferate or differentiate and, therefore, mediate tissue development, tissue regeneration and wound healing.[1] These biological processes require a molecularly dynamic ECM to allow spatiotemporal control over the display of signals.[2] A number of bioactive short peptide sequences have been identified over the past few decades which mimic these signals. The peptide sequence RGDS, found in the extracellular protein fibronectin, has been extensively investigated to develop artificial matrices. This sequence has been found to bind transmembrane integrin proteins to initiate the recruitment of multiple proteins giving rise to attachment domains to the cell's cytoskeleton, known as focal adhesions.[3] The formation of focal adhesions allows cells to spread and activate various pathways which results in gene expression. Studies have shown that the presence of the RGDS sequence conjugated to artificial matrices resolves in the formation of focal adhesions.[4] For example, attachment to such artificial matrices has been shown to induce adhesion and spreading of fibroblasts,[5] human mesenchymal stem cells [6], and human endothelial cells [7], among others.[8] Artificial matrices in which cues could be displayed dynamically would help to understand biological processes and enable the development of therapies for tissue regeneration.[9]* s-stupp@ northwestern. edu Homepage: http://stupp. northwestern. edu.
DOI: 10.1002/adfm.201203319
发表时间: 2013-08-12
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