The cellular glycocalyx is essential for conveying biochemical signals from the outside environment to cells during differentiation. For instance, glycosaminoglycans (GAGs), highly sulfated polysaccharides, recruit and present growth factors to their receptors, thus triggering downstream signaling and gene transcription. We are interested in recapitulating the unique functions of GAGs in synthetic materials, which can be delivered to the surface of living cells using a membrane engineering strategy. In a recent JACS paper, we have reported on how the glycocalyx of embryonic stem cells can be edited to promote neural differentiation.
Remodeling the glycocalyx with synthetic glycopolymers
Neural rosette differentiation of glycan-remodeled embryonic stem cells
Glycans are emerging as an important group of biomolecules for introducing functionality into synthetic tissue scaffolds. The vast structural diversity of glycans has precluded the establishment of clear guiding principles for de novo design of functional biomaterials to support artificial tissues and organs. We are developing high-throughput microarray platforms to directly link extracellular matrix glycan structures with cellular activity during embryonic stem cell differentiation. This approach allows the collective interrogation of concurrent signaling events in response to unique glycan microenvironments via individual glycans.
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Extracellular glycans orchestrate the formation of gradients of signaling factors in tissues during development. We are exploring glycan engineering strategies to spatially control growth factor signaling in complex three dimensional cellular systems, such as embryoid bodies or organoid precursors.