NSF/FDA SIR: Surface-Induced Self-Assembly of Fibrinogen Fibers: Designing Non- thrombogenic Materials and Understanding the Link Between Cholesterol and Thrombosis

摘要#1239560Rafailovich PI建议测试纤维蛋白原纤维是否在这些疏水区域自发成核，这可能解释了这种联系。他们建议通过产生脂质双层来模拟动脉壁，在双层中添加胆固醇和其他脂肪酸。然后，他们将使用SPM，结合拉曼和FTIR来确定木筏在纤维蛋白原吸附、纤维形成和血栓形成方面的作用。他们还将对不同类型的脂肪进行实验，结果将被用来筛选不同的治疗方法，以防止它们积累。拟议的工作将主要在FDA白橡树设施进行，与Katherine Vorvolakos博士和Dinesh Patwardhan博士合作。人类纤维蛋白原将在石溪大学分离和提纯，这是与丹尼斯·加拉纳基斯医学博士合作的一部分，丹尼斯·加拉纳基斯是SBU医院血库主任和公认的纤维蛋白原专家。加拉纳基斯博士对不同的纤维蛋白原组分和针对分子不同部分的抗体进行了清点。功能化聚合物将在Stony Brook合成，带到White Oak，在那里将准备旋转铸造基材并进行吸附实验。在SBU将制备包含脂肪筏的脂质双层膜，随后将在White Oak进行分析。

Abstract#1239560RafailovichThe PIs propose to test whether spontaneous nucleation of fibrinogen fibers occurs in these hydrophobic areas, possibly explaining this link. They propose to simulate the arterial wall by producing lipid bilayers, where cholesterol and other fatty acids are added. They will then use SPM, in conjunction with Raman and FTIR to determine the role of the rafts on fibrinogen adsorption, fibrilogenesis , and thrombosis. They will also experiment with different types of fats, and the findings will be used to screen different therapies to prevent their accumulation. The work proposed will be conducted mostly at the FDA, White Oak Facility, in collaboration with Drs. Katherine Vorvolakos and Dinesh Patwardhan. Human fibrinogen will be isolated and purified at Stony Brook University, as part of a collaboration with Dennis Gallanakis, MD, Director of the SBU Hospital Blood Bank and recognized expert on fibrinogen. Dr. Gallanakis keeps an inventory of different fibrinogen fractions and antibodies specific to different segments of the molecule. Functionalized polymers will be synthesized at Stony Brook, brought to White Oak where the spun cast substrates will be prepared and the adsorption experiments conducted. Lipid bilayer films with incorporated fat rafts will be prepared at SBU, and subsequent analysis which will be conducted at White Oak.