Mucin binding to bioactive molecules: physiologica.. (BIOMUC)
Mucin binding to bioactive molecules: physiological role and new biomaterials
Start date: Apr 1, 2012,
End date: Mar 31, 2015
Mucins are high molecular weight glycoproteins, responsible for most of the extraordinary properties of the mucosal layer, which covers around 300 m2 of our body’s surface. Mucins have mostly been studied in the context of their physiological role: for their ability to protect the epithelial layer from viral and bacterial infection, oxidative degradation, dehydration and mechanical stresses. They are also of major importance in cancer biology, where altered mucin secretions are recognized as cancer markers. A few studies have focused on the interactions of “objects” expected to diffuse from the exterior to the interior of the body through mucin gels, such as nutrients, antibodies, viruses and bacteria.This proposal describes how we will study the ability of mucin to sequester bioactive molecules secreted by cells surrounded by mucin. The goal is to investigate whether mucin gels can be a reservoir for bioactive molecules in a similar fashion to what the extracellular matrix is now recognized to be. The proposal describes a three-phase approach, which will both advance our knowledge on the physiological role of mucin gels and will lead to the development of innovative mucin-based biomaterials for drug delivery and tissue engineering applications.The first phase will focus on using 2D mucin coatings to study mucin interactions with relevant bioactive molecules. Also, structure/function will be investigated by modifying mucin chemistry. During the second phase, we will build multilayer thin films of hundreds of nanometer thick using lectin proteins as cross-linker between the mucin layers. The films will be characterized and their ability to act as a reservoir for drugs and other bioactive molecules will be assessed. Finally, in the return phase, we will combine the return host’s expertise on natural based polysaccharide gels, and the knowledge accumulated on mucins. In particular, 3D hydrogels comprising mucin will be developed as a new biomaterials.
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