UNS: Understanding protein adsorption in polysaccaride brushes

Colorado State University, Fort Collins CO

Investigators

Abstract

#1511830 Kipper, Matthew J. Many applications in medicine and biotechnology involve foreign surfaces that contact blood. Some applications involve long-term exposure to blood, such as heart valve replacements and stents. Other applications require intermediate-term or short-term contact. These include applications such as blood storage and medical procedures like dialysis and blood oxygenation. The materials used in these applications induce undesirable (and potentially catastrophic) blood-material interactions, such as blood clotting and inflammation. In fact, the only known surface that is compatible with flowing whole blood for long-term contact is the inside surfaces of blood vessels. This work will develop new surfaces that have chemical and structural features designed to mimic the inside surfaces of blood vessels. We will also study how the chemistry and structure of these new surfaces can be tuned to control interactions with important blood proteins that regulate blood-material interactions, like clotting. This will enable us to better design materials for blood-contacting applications. This work will prepare dense polymer brushes containing glycosaminoglycans, which are the polyanionic polysaccharides in the endothelial glycocalyx presented by the cells lining blood vessel walls. The interactions of important blood proteins with these glycocalyx mimics will be investigated by single-molecule fluorescence microscopy experiments. These experiments will be used to test new hypotheses about how blood-compatibility is determined by protein-surface interactions and protein-protein interactions at surfaces. Finally we will demonstrate that glycocalyx mimics result in reduced platelet adhesion and activation, and decrease the propensity for blood to clot. This work will lead to better understanding of the mechanisms whereby interactions of blood components with blood vessel walls prevent blood clotting. By understanding how the blood vessel wall prevents clotting we can better design blood-contacting surfaces for many applications in cardiovascular medicine and biotechnology. The findings from this research could also lead to advances in handling other complex protein mixtures in applications such as protein separation for the food and biopharmaceutical industries. Our education and outreach activities will include a one-week summer short course for middle school students, a symposium for a middle school students at a charter school that serves low-income and minority students, and contributions to a new textbook being authored by a co-PI.