Tunable Mucus-Inspired Bottlebrush Polymer Platform for Microbial Studies

Abstract Mucus is a critical component of the human immune system, creating a barrier against pathogenic infections and providing an environment that supports beneficial microbial communities. Mucins, the glycoproteins that form complex gel networks in mucus, leverage complex, multivalent interactions to tune their physicochemical properties, which impact their interaction with both commensal and pathogenic microbes. Because of the diversity of roles that mucus plays in biological systems, mucins themselves are so varied that it is impossible to fully replicate them. This limitation has hindered our ability to study mucosal structure–function–property relationships in vitro, especially as they relate to pathogenesis, and to deploy mucins for therapeutic applications. To overcome these barriers, we have developed a tunable, scalable platform that mimics key physical properties of mucus, supporting the standardization of studies and the application of a mucus-inspired polymer as a drug-delivery vehicle. Inspired by biological mucin synthesis, we report a bottlebrush polymer hydrogel platform capable of mimicking the macromolecular structure and function of these glycoproteins via redox-responsive cross-links and glycan presentation. The mechanical properties of this hydrogel are tunable and can be matched to the viscoelasticity of the mucus from diverse sources. Furthermore, no inherent microbial cytotoxicity is observed, enabling this platform to support in vitro studies of pathogen transport and growth in mucus-like systems. The ease of synthesis, structural control, and tunability afforded by this hydrogel will enable previously inaccessible studies of the mucosal environment and rational design of biosimilar hydrogels to support human health.