Ion-mediated effects of glycosylation on the disordered mucin domain: Insights from coarse-grained simulations.

Mucins are essential glycoproteins that form the backbone of mucus, a hydrogel protecting epithelial surfaces throughout the body. Their biophysical properties are governed by the densely glycosylated and highly disordered proline-threonine-serine (PTS) mucin domain, which becomes negatively charged by the addition of terminal sialic acid and sulfate groups to its glycans. The properties of mucins are further modulated by their interactions with cations, particularly sodium and calcium, which influence mucus expansion and viscoelasticity. Alterations in mucin glycosylation patterns or cation interactions contribute to the development of various pathological conditions. Modulating mucin's functional relationships to ameliorate these conditions requires first obtaining a detailed understanding of its structure; however, the large size, extensive disorder, and polymeric nature of mucins present significant challenges to their structural characterization. Here, we employed a coarse-grained modeling approach to investigate the effects of glycosylation, glycan charge, and salt concentration on mucin PTS organization. Using two different glycan structures, we explored how their interactions with monovalent (Na