Virus-Inspired Particle Coatings: Tunable Specific Multivalent Interactions with Mucus Barriers

We report direct sensitive measurements of separation dependent interactions and diffusivities of polymer coated colloids on mucin layers. With inspiration from viral capsid surface chemistries, grafted polyzwitterionic layers on the colloidal particles have terminal boronic acid moieties that are known to have pH dependent binding with sialic acid groups on mucins. By nonintrusively measuring and analyzing Brownian collisions between functionalized micron sized colloids with mucin layer surfaces using total internal reflection microscopy (TIRM), we directly measure nonspecific steric interactions and specific binding of boronic acids to mucin tethers as a function of pH in physiological media with nanometer- and kT-scale resolution. The measured interactions reveal pH tunable attraction between the colloidal coatings and mucin layers mediated by a hierarchical multivalent mechanism based on multiple wormlike chain mucin tethers per particle and multiple molecular bonds per mucin tether. Steric interactions are consistent with prior studies of polymer-mucin interactions, and wormlike chain tethers are well described by interaction potentials using independently characterized mucin chain parameters. Measurements of shear mediated detachment of tethered particles at each pH reveal the rupture of mucin tethers in the presence of pN-scale hydrodynamic forces relevant to physiological flow rates. The net pH dependent interactions between particle coatings and mucin layers vary from completely repulsive to varying kT-scale attraction, providing a route to design nanoparticle coatings with specific interactions for optimal transport across mucus barriers at different pHs.