Mucus‐inspired low‐fouling barriers based on self‐assembled glycopeptide nanofibers

Abstract

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. However, mucus glycoproteins (i.e., “mucins”) derived from natural sources are highly variable and recombinant mucin production is impractical, which has led to increasing interest in synthetic mucin analogs. Here we report synthetic 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. Carbohydrates decorating the surface of glycopeptide nanofibers are specifically recognized by their cognate lectins. Additionally, the type of carbohydrate appended onto the nanofiber can be 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”) (Figure 1a–b). 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 E. coli adhesion by ~90%, whereas non‐glycosylated peptide hydrogels only reduced bacterial adhesion by 50%. Additionally, glycopeptide hydrogels coated on glass robustly inhibited adhesion of macrophages (Figure 1c) and fibroblasts (Figure 1d) in the presence of serum, whereas non‐glycosylated peptide hydrogels were permissive to non‐specific cell adhesion. Together, these data demonstrate that self‐assembling glycopeptides can provide synthetic barriers with selective macromolecule permeability and resistance to non‐specific cell interactions similar to natural mucinous gels. Moving forward, we anticipate that 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.Support or Funding InformationNSF Career award, DMR‐1455201This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.