Mucus is a complex fluid that maintains moisture and simultaneously acts as a barrier and facilitates transport of select materials between the body and adjacent fluids. While mucus is comprised primarily of water, it is highly heterogeneous containing the biopolymer mucin along with lipids, salts, DNA, proteins, and cells. Complex mechanisms control the reversible network formation observed in mucus and mucin solutions. Some isolated relationships between biopolymer network structure, pH and ionic strength, and rheology have been identified; however, a complete understanding of the interplay in these mechanisms is lacking. In this effort, rheology of native mucus and mucin solutions was examined as a function of pH and salt concentration. Bulk rheology of native and artificial lung mucus confirmed that native mucus displays a solid-like behavior at low strain values. Mucus displays this solid-like gel behavior at pH values ca. 4 and below, and displays solution behavior at higher pH values. Ion concentration also plays an important role with divalent cations (Ca2+) reducing the viscosity of gelled mucin and increasing the viscosity of solution-state mucin. In addition to rheological characterization, mucin-mucin and mucin-solute interactions and resultant changes in microstructure were also studied. Morphological and chemical changes at the nano-scale were correlated to the micro-structural changes observed with rheology. Dynamic light scattering showed mucin polymer particle size heterogeneity as well as a significant increase in particle size at pH values ca. 4 and below — where the solutions display a gel behavior. Using zeta potential a decrease in dispersive forces was observed that allows for polymer-polymer interaction and particle aggregation at low pH values. Atomic force micrography showed spheroid-like aggregates between adjacent mucin particles under acidic conditions. The ability to understand and control the reversible association of network structures in polymer and biopolymer systems, such as mucin, through supramolecular interactions has fundamental impacts in the field of polymer science and engineering. There is also significant potential to advance applications involving novel hydrogel materials, such as disease treatments and drug delivery.