Synthesis, biophysical characterization and virus penetration of mucus-inspired dynamic hydrogels

We will synthesize and biophysically characterize novel mucin-inspired hydrogels mimicking native mucus biobarriers. The architecture and composition of the alveolar lining layer in the lung (not drawn to scale) with glycocalyx, surfactant components, and mechanical microenvironment mucus biobarriers. Our hypothesis is that an optimal mucus hydrogel is formed by crosslinking of semi-flexible glycopolymers (mucins) and has evolved to exhibit pore size distributions matching the size range of many respiratory viruses in order to efficiently block particle penetration. Our synthetic mucins, consisting of high
molecular weight dendronized polyanionic glycopolymers, will allow for efficient interaction with viral surface proteins, which will be examined using an exemplary respiratory virus, the influenza A virus (IAV). We will develop biophysical assays employing total internal reflection fluorescence (TIRF) microscopy or microfluidics
to probe how IAVs interact with native and synthetic mucus hydrogels. In particular, we will investigate how the IAV envelope protein neuraminidase, which interacts with and possibly destabilizes mucus components, affects the penetration behavior of IAVs in native and synthetic mucus hydrogels. The detailed knowledge of
these interactions will then be used to optimize virus blocking strategies by refining the design of our synthetic mucus components.