Nanoscale materials for probing the biological functions of the glycocalyx

Glycans are among the most intriguing carriers of biological information in living systems. The structures of glycans not only convey the cells' physiological state, but also regulate cellular communication and responses by engaging receptors on neighboring cells and in the extracellular matrix. The assembly of simple monosaccharide building blocks into linear or branched oligo- and polysaccharides gives rise to a large repertoire of diverse glycan structures. Despite their structural complexity, individual glycans rarely engage their protein partners with high affinity. Yet, glycans modulate biological processes with exquisite selectivity and specificity. To correctly evaluate glycan interactions and their biological consequences, one needs to look beyond individual glycan structures and consider the entirety of the cell-surface landscape. There, glycans are presented on protein scaffolds, or are linked directly to membrane lipids, forming a complex, hierarchically organized network with specialized functions, called the glycocalyx. Nanoscale glycomaterials, which can mimic the various components of the glycocalyx, have been instrumental in revealing how the presentation of glycans can influence their biological functions. In this review, we wish to highlight some recent developments in this area, while placing emphasis on the applications of glycomaterials providing new insights into the mechanisms through which glycans mediate cellular functions.