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

Nat Chem Biol

Department of Biomedical Engineering, The Johns Hopkins University, 3400 N. Charles Street, Clark Hall 106A, Baltimore, Maryland 21218, USA.

Published: March 2006

AI Article Synopsis

  • Researchers have developed a method using N-acetyl-D-mannosamine (ManNAc) analogs to modify the surface properties of living cells, particularly their glycocalyx.
  • A specific analog called Ac(5)ManNTGc allows the expression of thiols on cell surfaces, leading to better cell clustering and adhesion to specially treated substrates.
  • The effects of this analog can influence stem cell behavior, promoting characteristics associated with neuronal differentiation, and are affected by the type of substrate the cells are grown on, with better results observed on gold compared to glass.

Article Abstract

Metabolic 'oligosaccharide engineering' methods based on N-acetyl-D-mannosamine (ManNAc) analogs allow the glycocalyx of living cells to be remodeled. 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, Ac(5)ManNTGc 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.

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Source
http://dx.doi.org/10.1038/nchembio770DOI Listing

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