| dc.description.abstract | Mucus is a ubiquitous hydrogel that coats all epithelial cell surfaces. Once thought to be an inert hydrogel, the mucosal barrier is now recognized as a critical component of the innate immune system. It serves not only as a physical and chemical barrier against foreign objects, pathogens, and environmental stressors, but also as a selective interface that shapes an organism’s microbiome. Many of these functions are mediated by the primary structural component of mucus: the mucin protein. Mucins are large, densely glycosylated proteins, with carbohydrates contributing up to 80% of their molecular weight. In addition to mediating microbial interactions, mucins contribute to the biophysical properties of mucus that enable lubrication, adhesion, and protection of tissues. Beyond their physical responsibilities, mucins modulate virulence of microbes, promote cultivation of commensal bacteria through adhesion points and nutrient presentation, and mediate critical immune modulations of the host. However, molecular-level insights remain lacking in understanding mucin structure as well as function. The large size and heterogeneity of mucins and their glycosylation have made it challenging to parse the individual contributions of mucin structural features to biological function. Synthetic mucin mimics, developed using polymer chemistry, offering a promising strategy to probe these structure–function relationships by enabling precise control over molecular weight, glycan identity and density, polymer architecture, and morphology. To address these challenges, we developed novel synthetic mucins to elucidate mucin structure–function relationships. Emphasizing the importance of mucin’s extended morphology, we designed new synthetic strategies to isolate and investigate the impact of mucin structural motifs, such as anionic glycan identity and bottlebrush architectures, on synthetic mucin morphology (Chapter 2). We next demonstrated that synthetic mucins can provide insight into the glycan-binding preferences of probiotic bacteria, highlighting the roles of mucins in shaping microbial organization within the microbiome and emphasizing the potential of synthetic mucins as prebiotics (Chapter 3). Finally, recognizing that mucins key modulators of microbial virulence and infection, we explored the potential of synthetic mucins as antibacterial scaffolds capable of delivering therapeutic cargoes. This work emphasized the importance of understanding how polymer structure influences biological activity and targeting capabilities (Chapter 4). Ultimately, we anticipate that the synthetic mucin platform developed in this work will help address fundamental questions in mucin biology and advance the development of mucin-inspired therapeutic materials. | |
