Direct Measurement of Macromolecule-Coated Colloid-Mucus Interactions

We report measurements of macromolecule-coated colloids interacting with mucus to understand colloidal particle diffusion near mucus-coated surfaces. Total internal reflection microscopy is used to measure colloids with adsorbed poly(ethylene glycol) (PEG), bovine serum albumin (BSA), and polyelectrolyte bilayers (PEB) interacting with mucus to obtain kT-scale energy landscapes and nanometer-scale diffusivity landscapes. Energy landscapes are quantified as a superposition of van der Waals, steric, and tethering potentials, and diffusivity landscapes are modeled by considering lubrication in the presence of permeable layers. PEG- and BSA-coated colloids have soft repulsion with mucus that could enable diffusion of small particles within mucus pores. PEB-coated colloids display attractive tethers to mucus that produce irreversible binding. Different interaction potentials for each particle coating confirm that the ζ-potential is not a successful predictor of particle-mucus interactions and diffusion. Diffusivity landscapes show thick mucus layers are permeable to the solvent and dominate particle-mucus hydrodynamic interactions relative to the thin, impermeable particle coatings. Our results show direct measurements and models to understand how particle coating properties (e.g., elasticity, porosity) control particle interactions and transport near mucus films to potentially aid the design of better particle-based therapeutics and diagnostics.