Investigating mucin interactions with diverse surfaces for biomedical applications

Sammanfattning: Mucous membranes are covered with mucus, a viscoelastic hydrogel that plays an essential role in their protection from shear and pathogens. The viscoelasticity of mucus is owing to mucins, a group of densely glycosylated proteins. Mucins can interact with a wide range of surfaces; thus, there is big interest in exploring and manipulating such interactions for biomedical applications. This thesis presents investigations of mucin interactions with hydrophobic surfaces in order to identify the key features of mucin lubricity, as well as describes the development of materials that are optimized to interact with mucins. In Paper I we investigated the domains which make mucins outstanding boundary lubricants. The results showed that the hydrophobic terminal domains of mucins play a crucial role in the adsorption and lubrication on hydrophobic surfaces. Specifically, protease digestion of porcine gastric mucins and salivary mucins resulted in the cleavage of these domains and the loss of lubricity and surface adsorption. However, a “rescue” strategy was successfully carried out by grafting hydrophobic phenyl groups to the digested mucins and enhancing their lubricity. This strategy also enhanced the lubricity of polymers which are otherwise bad lubricants. In Paper II we developed mucoadhesive materials based on genetically engineered partial spider silk proteins. The partial spider silk protein 4RepCT was successfully functionalized with six lysines (pLys-4RepCT), or the Human Galectin-3 Carbohydrate Recognition Domain (hGal3-4RepCT). These strategies were aiming to either non-specific electrostatic interactions between the positive lysines and the negative mucins, or specific binding between the hGal3 and the mucin glycans. Coatings, fibers, meshes and foams were prepared from the new silk proteins, and the adsorption of porcine gastric mucins and bovine submaxillary mucins was measured, demonstrating enhanced adsorption. The work presented demonstrates how mucin-material interactions can provide us with valuable information for the development of new biomaterials. Specifically, mucin-based and mucin-inspired lubricants could provide desired lubrication to a wide range of surfaces, while our new silk based materials could be valuable tools for the development of mucosal dressings.