Mucus is a glycoprotein-rich gel that protects epithelial tissue surfaces from non-specific interactions with micro-organisms and macromolecules. Synthetic mucus-like barriers could enable new opportunities to confer implantable materials with non-fouling properties that are essential for biocompatibility and long-term efficacy. Unfortunately, mucus glycoproteins (i.e., “mucins”) derived from natural sources are highly variable and difficult to purify, while recombinant mucin production is impractical. To circumvent these challenges, here we report synthetic mucin analogs based on carbohydrate-modified peptides (i.e., “glycopeptides”) that self-assemble into beta-sheet nanofibers in water. The dense carbohydrate coating on the surface of glycopeptide nanofibers is similar to that of naturally derived mucins. Likewise, carbohydrates decorating the surface of glycopeptide nanofibers can be selectively recognized by their cognate lectins. Finally, the type of carbohydrate appended onto the nanofiber can be selectively and efficiently varied via glycosyltransferase enzymes. Using this approach, we synthesized nanofibers decorated with n-acetylglucosamine (GlcNAc) and n-acetyllactosamine (LacNAc) that selectively bind to wheat germ agglutinin (WGA) and galectins, respectively. At millimolar concentrations in water, glycopeptide nanofibers entangled into viscoelastic hydrated gels (i.e., “hydrogels”). GlcNAc-decorated glycopeptide hydrogels bound and retained WGA, but were permeable to various non-lectin proteins, including albumin and green fluorescent protein, as well as the mannose-binding lectin, concanavalin A. GlcNAc-decorated glycopeptide hydrogels coated onto a glass surface reduced <i>E. coli </i>adhesion by ~90%, whereas non-glycosylated peptide hydrogels only reduced bacterial adhesion by 50%. Additionally, glycopeptide hydrogels coated on glass completely inhibited NIH3T3 fibroblast adhesion in the presence of serum, whereas non-glycosylated peptide hydrogels were permissive to non-specific fibroblast adhesion. Together, these data demonstrate self-assembly of glycopeptides into hydrogels with selective macromolecule permeability and resistance to non-specific cell interactions that is similar to natural mucinous gels. Moving forward, we anticipate that self-assembled glycopeptide hydrogels will be broadly useful as mucus-inspired surface coatings to improve the biocompatibility and efficacy of implantable devices, drug delivery vehicles, and biosensors.

Self-assembling glycopeptide hydrogels as selectively permeable mucus-like barriers

255th National Meeting (2018)

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