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

Metabolic 'oligosaccharide engineering' methods based on N -acetyl- D -mannosamine (ManNAc) analogs allow the glycocalyx of living cells to be remodeled 1 , 2 , 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, Ac 5 ManNTGc induced β-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.