Synthetic Mucin Mimetics: Nanoscale Tools for Glycobiology

Mucins are long and densely glycosylated cell-surface proteins that mediate a number of critical biological events. For example, they protect the cell surface and serve as mediators of cellular communication. Despite the importance of mucins, very little is known about the molecular mechanisms of their function. This is mainly due to the complexity and glycan micro-heterogeneity inherent to mucins structures. Creating well-defined mucins has been a long-standing problem because unlike other biomaterials, glycans are metabolic products and outside the immediate purview of the genome. Inspired by mucins, we have developed synthetic materials that emulate the architecture and function of these glycoproteins but afford control over glycan structure, valency and presentation. We have now generated a number of mucin mimetics endowed with useful functionalities for their integration with synthetic materials as well as living cells. In my presentation, I will show that mucin mimetic microarrays can be used to evaluate in a high-throughput manner how parameters, such as the valency of mucins and their spatial separation, determine the modes of their interactions with receptors. I will also show that mucin mimetics can be introduced into the Glycocalyx (i.e., the network of polysaccharides on the cell surface) of living cells to perturb the biophysical properties of the cell-surface and, consequently, its interactions with the surrounding matrix.