Metabolic installation of thiols into sialic acid modulates adhesion and stem cell biology

被引:118
作者
Sampathkumar, SG [1 ]
Li, AV [1 ]
Jones, MB [1 ]
Sun, ZH [1 ]
Yarema, KJ [1 ]
机构
[1] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA
关键词
D O I
10.1038/nchembio770
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
Metabolic 'oligosaccharide engineering' methods based on N-acetyl-D-mannosamine (ManNAc) analogs allow the glycocalyx of living cells to be remodeled(1-3). Herein we report the analog Ac(5)ManNTGc (1) that enables thiols to be expressed in surface sialic acids. By locating this versatile functional group on the outer periphery of normally nonadhesive human Jurkat cells, we obtained spontaneous cell-cell clustering and attachment to complementary maleimide-derivatized substrates. When analyzed in human embryoid body-derived (hEBD) stem cells, Ac5ManNTGc induced beta-catenin expression and altered cell morphology, consistent with neuronal differentiation. Notably, these effects were modulated by the growth substrate of the cells, with a stronger response observed on a gold surface than on glass. Together, these results establish sugar analogs as small-molecule tools for tissue engineering by providing a method for attaching cells to scaffolds via their surface carbohydrates as well as offering a means to influence stem cell fates.
引用
收藏
页码:149 / 152
页数:4
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