UNS: Understanding protein adsorption in polysaccaride brushes

UNS：了解多糖刷中的蛋白质吸附

• 批准号: 1511830
• 负责人: Matthew Kipper
• 金额: $ 40万
• 依托单位: Colorado State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2019-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1511830&HistoricalAwards=false
• 关键词: UNS; Understanding; protein; adsorption; polysaccaride

#1511830Kipper, 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.

#1511830马修·J·基珀#1511830在医学和生物技术中的许多应用都涉及接触血液的异物表面。一些应用包括长期接触血液，如心脏瓣膜置换和支架。其他应用程序需要中期或短期接触。这些应用包括血液储存以及透析和血液充氧等医疗程序。这些应用中使用的材料会导致不良的(可能是灾难性的)血液-材料相互作用，如血液凝结和炎症。事实上，唯一已知的与流动的全血长期接触的表面是血管的内表面。这项工作将开发具有化学和结构特征的新表面，旨在模仿血管的内表面。我们还将研究如何调整这些新表面的化学和结构，以控制与重要血液蛋白质的相互作用，这些蛋白质调节血液与物质的相互作用，如凝血。这将使我们能够更好地设计用于血液接触的材料。这项工作将制备含有糖胺多聚糖的致密聚合物刷子，糖胺多糖是血管壁内皮细胞呈递的内皮糖萼中的多阴离子多糖。我们将通过单分子荧光显微镜实验来研究重要的血液蛋白与这些糖基化模拟物之间的相互作用。这些实验将被用来测试关于血液相容性如何由蛋白质-表面相互作用和蛋白质-蛋白质表面相互作用决定的新假说。最后，我们将证明，模拟糖基化可以减少血小板的黏附和激活，降低血液凝结的倾向。这项工作将有助于更好地理解血液成分与血管壁相互作用防止血液凝结的机制。通过了解血管壁如何防止凝血，我们可以更好地为心血管医学和生物技术中的许多应用设计与血液接触的表面。这项研究的发现还可能导致在处理食品和生物制药行业的蛋白质分离等应用中处理其他复杂蛋白质混合物的进展。我们的教育和外展活动将包括为中学生举办为期一周的暑期短期课程，为一所服务于低收入和少数族裔学生的特许学校的中学生举办座谈会，以及为一名合作者正在编写的新教科书做出贡献。