Engineering of spectator glycocalyx structures to evaluate molecular interactions at crowded cellular boundaries
Year: 2019
Type: article
Abstract: In the mucosal epithelium, the cellular glycocalyx can project tens to hundreds of nanometers into the extracellular space, erecting a physical barrier that provides protective functions, mediates the exchange of nutrients and regulates cellular interactions. Little is understood about how the physical properties of the mucosal glycocalyx influence molecular recognition at the cellular boundary. Here, we report the synthesis of PEG-based glycopolymers with tunable glycan composition, which approximate the extended architecture of mucin glycoproteins, and tether them to the plasma membranes of red blood cells (RBC) to construct an artificial mucin brush-like glycocalyx. We evaluated the association of two lectins, ConA and SNA, with their endogenous glycan ligands on the surface of the remodelled cells. The extended glycocalyx provided protection against agglutination of RBCs by both lectins; however, the rate and magnitude of ConA binding were attenuated to a greater degree in the presence of the glycopolymer spectators compared to those measured for SNA. The different sensitivity of ConA and SNA to glycocalyx crowding likely arises from the distinct presentation of their mannoside and sialoside receptors, respectively, within the native RBC glycocalyx.
Source: Faraday Discussions
DOI: 10.1039/c9fd00024k
Institution: University of California San Diego
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Alfred P. Sloan Foundation, Research Corporation for Science Advancement, National Institutes of Health, University of California, San Diego, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, Division of Electrical, Communications and Cyber Systems, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1589343018, G1699492418, G1884000469, G2041273731, G252083234, Glycan array for phenotype-driven capture and genotyping of viruses in primary isolates, G3033040839, G3053085007, NNCI: San Diego Nanotechnology Infrastructure (SDNI), G5285237269, G5523730667, In vivo glycan engineering at the cell-matrix interface to control stem cell fate, University of California San Diego Neuroscience Microscopy Imaging Core, G8448096725, G9000255603
OpenAlex ID: W2940206405