Antibody-mediated trapping in biological hydrogels is governed by sugar-sugar hydrogen bonds

N-glycans on IgG and IgM antibodies (Ab) facilitate Ab-mediated crosslinking of viruses and nanoparticles to the major structural elements of mucus and basement membranes. Nevertheless, the chemical moieties in these biological hydrogel matrices to which Ab can bind remain poorly understood. To gain insights into the chemistries that support Ab-matrix interactions, we systematically evaluated IgG- and IgM-mediated trapping of nanoparticles in different polysaccharide-based biogels with unique chemical features. In agarose, composed of alternating d-galactose and 3,6-anhydro-l-galactopyranose (i.e. hydroxyl groups only), anti-PEG IgM but not anti-PEG IgG trapped PEGylated nanoparticles. In alginate, comprised of homopolymeric blocks of mannuronate and guluronate (i.e. both hydroxyl and carboxyl groups), both IgG and IgM trapped PEGylated nanoparticles. In contrast, chitosan, comprised primarily of glucosamine (i.e. both hydroxyl and primary amine groups), did not facilitate either IgG- or IgM-mediated trapping. IgG-mediated trapping in alginate was abrogated upon removal of IgG N-glycans, whereas IgM-mediated trapping was eliminated in agarose but not alginate upon desialylation. These results led us to propose a model in which hydrogen bonding between carboxyl and hydroxyl groups of glycans on both Ab and matrix facilitates Ab-mediated trapping of pathogens in biogels. Our work here offers a blueprint for designing de novo hydrogels that could harness Ab-matrix interactions for various biomedical and biological applications. STATEMENT OF SIGNIFICANCE: Here, we interrogated the molecular mechanism of antibody-mediated trapping to address what are the chemical moieties on biogels that are essential for facilitating trapping in biogels. We systematically evaluated the potencies of IgG and IgM to trap nanoparticles in different polysaccharide-based biogels with unique and highly defined chemical moieties: hydroxyl groups (agarose), amine groups (chitosan), and carboxyl groups (alginate). We discovered that only hydroxyl/carboxyl hydrogen bonds (and stronger) are sufficiently strong enough to facilitate antibody-mediated trapping; weaker hydroxyl/hydroxyl bonds or hydroxyl/amine bonds fail to adequately slow particles. Our findings presents the first blueprint for how to engineer de novo biogels that are capable of harnessing antibodies to immobilize foreign entities in the biogels, for applications ranging from infectious disease to contraception to purification processes.