(187a) At the Interface of Immunology and Engineering: Elucidating the Biophysical and Molecular Interactions of Pathogens and Polymers with the Immune System

This presentation will explore our lab’s recent progress in elucidating (i) a novel and exceptionally potent mechanism of mucosal immunity based on transient antibody-mucin interactions, and (ii) the interactions between PEGylated nanoparticles and the immune system.  More antibodies are secreted into mucus than either the blood or the lymph, yet the mechanisms by which antibodies can protect against pathogens in mucus are not fully understood.  Using high resolution fluorescence microscopy, we reveal that the array of pathogen-bound antibodies can trap individual pathogens in the mucin matrix at sub-neutralizing antibody concentrations through N-glycans on the Fc-domain.  The carefully tuned antibody-mucin affinity transforms the mucus gel into an effective adhesive barrier against a diverse array of viral and bacterial pathogens in vitro and in vivo.  We are developing computational models to further reveal the dynamics of this ‘molecular shield’.  Separately, we are exploring how the physicochemical properties of polymeric coatings on nanoparticles may influence their interactions with immune cells and antibodies. Using nanoparticles with precisely tunable polymer grafting, we show that evading immune cell uptake and clearance in mice requires PEG grafting at densities substantially exceeding the minimum for polymer brush conformation.