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利用主体-客体策略模拟糖基化胶原蛋白缀合物以改变表型细胞迁移和体内伤口愈合。

Modeling Glyco-Collagen Conjugates Using a Host-Guest Strategy To Alter Phenotypic Cell Migration and in Vivo Wound Healing.

机构信息

Indian Institute of Science Education and Research , Dr. Homi Bhabha Road, Pune 411008, India.

出版信息

ACS Nano. 2017 Dec 26;11(12):11969-11977. doi: 10.1021/acsnano.7b01789. Epub 2017 Dec 6.

DOI:10.1021/acsnano.7b01789
PMID:29077384
Abstract

The constructs and study of combinatorial libraries of structurally defined homologous extracellular matrix (ECM) glycopeptides can significantly accelerate the identification of cell surface markers involved in a variety of physiological and pathological processes. Herein, we present a simple and reliable host-guest approach to design a high-throughput glyco-collagen library to modulate the primary and secondary cell line migration process. 4-Amidoadamantyl-substituted collagen peptides and β-cyclodextrin appended with mono- or disaccharides were used to construct self-assembled glyco-collagen conjugates (GCCs), which were found to be thermally stable, with triple-helix structures and nanoneedles-like morphologies that altered cell migration processes. We also investigated the glycopeptide's mechanisms of action, which included interactions with integrins and cell signaling kinases. Finally, we report murine wound models to demonstrate the real-time application of GCCs. As a result of our observations, we claim that the host-guest model of ECM glycopeptides offers an effective tool to expedite identification of specific glycopeptides to manipulate cell morphogenesis, cell differentiation metastatic processes, and their biomedical applications.

摘要

构建和研究结构定义明确的同源细胞外基质(ECM)糖肽的组合文库可以显著加速鉴定参与各种生理和病理过程的细胞表面标志物。在这里,我们提出了一种简单可靠的主体 - 客体方法来设计高通量糖胶原文库,以调节原代和次代细胞迁移过程。用 4-氨基金刚烷取代的胶原蛋白肽和带有单糖或二糖的β-环糊精来构建自组装糖胶原缀合物(GCC),发现它们具有热稳定性,具有三螺旋结构和纳米针状形态,改变细胞迁移过程。我们还研究了糖肽的作用机制,包括与整合素和细胞信号激酶的相互作用。最后,我们报告了鼠伤口模型,以证明 GCC 的实时应用。根据我们的观察结果,我们声称 ECM 糖肽的主体 - 客体模型提供了一种有效的工具,可加速鉴定特定糖肽以操纵细胞形态发生、细胞分化转移过程及其生物医学应用。

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