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

In the first funding period, we developed a methodology for synthesis of high molar mass dendronized polysulfates (mucin-inspired polymers, MIPs). MIPs showed mucin-like elongated single-chain fiber in cryo-electron tomography of 200 nm and appeared as potential antiviral against sulfate-binding viruses such as HSV-1, RSV and SARS-CoV-2. After crosslinking, MIPs formed synthetic hydrogels that mimicked the viscoelastic properties of healthy sputum. In order to quantify the barrier function of native mucus and of mucus-inspired hydrogels, we developed (with B04|Siegmund/Weinhart and B05|Fulde/Forslund/Schaupp) an imaging framework, which enables to follow the motion of fluorescently labelled bacteria above, within, and across a mucus layer grown on confluent epithelial cells. This approach enabled to follow bacterial motion in a fixed imaging plane with very high resolution, but an extension to 3-dimensional tracking of single bacteria was possible but notably limited by the microscope’s temporal resolution.