Despite the crucial roles of glycan structures in glycosylated macromolecules such as proteoglycans in the extracellular matrix, their regulatory mechanism is still poorly understood, due to the complex structures and dynamic interactions of polysaccharides. Here, supramolecular polymers were employed as simplified mimics for fibrous proteoglycans to investigate the regulatory role of the glycans. We constructed a series of glycopeptides based on the precise linear tetrasaccharide structure (CT) from chondroitin. Experimental and computational results indicated that glycopeptides containing triphenylalanine and chondroitin tetrasaccharide (CT-3F) could assemble into tetra-stranded nonhelical fibers. Compared with the glycopeptide fiber of nonlinear sialyllactose (SL-3F), the linear geometry of CT resulted in fewer hydrogen bonds than nonlinear SL, and consequently different flexibility of the corresponding supramolecular glycopolymers which was supported by the change of measured persistence length and bending modulus. Importantly, flexibility of CT-3F fibers from glycan geometry could significantly enhance their interaction with preosteoblastic cells and osteogenic gene expression. These results reveal an unexplored dimension of complex oligosaccharides and provide an alternative pathway for tuning the properties of supramolecular polymers and even related biomaterials.
Liu et al. (Thu,) studied this question.