Glycosaminoglycans (GAGs) are linear, sulfated polysaccharides integral to crucial physiological processes, influencing cell division, cancer metastasis, angiogenesis, and neuronal development. For example, specific sulfation motifs on chondroitin sulfate GAGs (CS-E) stimulate neurotrophin growth factor receptors, enhancing neurite outgrowth. However, studying these complex GAGs on cell surfaces is challenging. A novel approach has been developed to display specific sulfated GAG structures on cell surfaces using a liposomal fusion strategy. Tailoring membranes with CS-E activates growth factor-mediated signaling pathways, allowing fine-tuned modulation of neuronal growth. This approach demonstrates that chemically controlling exogenous glycan presentation on cell surfaces can lead to sustained effects on cellular signaling and function. These findings illustrate the potential of glycan engineering to influence complex cellular events and provide a powerful tool for remodeling cell membranes with a variety of biomolecules. This advancement has the potential to impact fields such as neurobiology, cancer research, and drug development.
Fig.1 (A) CS polysaccharide structures used in this study. n≈110. (B) Strategy to remodel cell surfaces with CS GAGs and control signaling pathways. (Pulsipher, et al., 2014)
CD BioGlyco has developed a powerful, synthetically facile method to display large, complex polysaccharides on cell surfaces using chemically modified liposomes. This service controls the surface density, as well as the specific glycan structure to activate key intracellular signaling pathways and induce functional responses in a dose-dependent manner. The presentation of CS polysaccharides enriched in a specific sulfation motif can trigger Akt signaling pathways and exert sustained effects on neuronal growth. Figure 2 lists the standard stypes for displaying complex polysaccharides on cell surfaces via liposome fusion.
Moreover, CD BioGlyco also provides Fluorophore-based Liposome Fusion Cell Surface Glycoengineering Service and Hydrophobic Membrane Insertion-based Cell Surface Glycoengineering Service based on the liposome fusion technology. Clients can find other Cell Surface Glycoengineering Services on our websites which bring custom solutions to help our clients study the field of glycobiology.
Fig.2 The flowchart of displaying complex polysaccharides on cell surfaces process. (CD BioGlyco)
Publication Data
Technology: Cell surface engineering, metabolic oligosaccharide engineering, de novo glycan display.
Journal: Cell Chemical Biology
IF: 8.6
Published: 2016
Results: De novo glycan display is a revolutionary advancement, facilitating the creation of a biologically relevant model for studying developing neurons in the hippocampus. Certain sulfated motifs on chondroitin sulfate glycosaminoglycans (CS GAGs) have been discovered to stimulate the growth of embryonic hippocampal neurons by recruiting growth factors to the cell surface and enhancing receptor activation. Previous research relied on artificial substrates for CS GAG presentation, limiting its physiological relevance. A novel approach using liposomes has been introduced to mimic the natural presentation of CS GAGs on neuronal surfaces, enabling precise control of neuronal signaling pathways and cellular responses through specific sulfation motifs. This technique has broader applications, including influencing stem cell differentiation by activating stem cell signaling pathways with synthetic glycomimetics.
Fig.3 De novo display of cell-surface glycans. (Griffin & Hsieh-Wilson, 2016)
This general strategy can be extended to perform comparative analyses of the effects of various glycans on cellular signaling and function. Moreover, the use of targeted liposomal delivery strategies both in vitro and in vivo will expand the application of this approach to many important biological contexts, such as neurodegeneration, stem cell differentiation, and cancer.
CD BioGlyco is a company with extensive glycan chemistry research experience and aims to be clients' best glycan research cooperator. Based on our Glycoengineering Platform, we have the ability to offer a suitable protocol for the GAGs-based liposome fusion service. If you are interested in our services, please feel free to contact us for more information.
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