HETEROGENEOUS NUCLEATION AND SICKLE CELL DISEASE

异质成核和镰状细胞病

• 批准号: 2030791
• 负责人: FRANK A FERRONE
• 金额: $ 17.46万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-20 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2030791
• 关键词: animal tissue; biophysics; chemical kinetics; erythrocytes; hemoglobin F; hemoglobin Ss; lasers; mutant; nucleolus; oxygen transport; photolysis; polymerization; polymers; sickle cell anemia; video microscopy

DESCRIPTION: Adapted from the investigator s abstract: Sickle cell disease arises from the polymerization of sickle hemoglobin by a double nucleation mechanism involving homogenous nucleation in solution and heterogeneous nucleation into sickle hemoglobin polymer surfaces. While the conceptual features of that mechanism have been validated, its predictive power is limited by the lack of a structural foundation and a flawed description of heterogeneous nucleation in the presence of non-polymerizing molecules. The experimental core of this proposal is to assemble a data base of solubility (csat), homogeneous and heterogeneous nucleation rates and elongation rates, for sickle hemoglobin assembly as a function of solution conditions (T, pH, non-ideality) and for various amino acid substitutions. Sickle hemoglobin mutants with additional amino mutations will primarily be provided by Dr. James Manning of Rockefeller University, and the hemoglobin of the SAD mouse will be provided by Dr. Frank Costantini of Columbia University. These data will be used to test and refine a new structural model for heterogeneous nucleation which are proposed herein. The data will also allow the description of heterogeneous nucleation to be extended to describe gelation in the presence of oxygen, fetal Hb, or other non-polymerizing species. This work will ultimately provide an energetic map of the interactions which create the rigid, vasoocclusive gel.

描述：改编自S研究员摘要：镰状细胞病 由双成核的镰状血红蛋白聚合而成 溶液中均相成核和非均相成核机理 成核形成镰刀状的血红蛋白聚合物表面。虽然概念性的 该机制的功能已经得到验证，其预测能力是 受限于缺乏结构基础和对 在非聚合分子存在下的非均相成核。 这一建议的实验核心是汇编一个数据库 溶解度(Csat)、均相成核速率和非均相成核速率 作为溶液函数的镰状血红蛋白组件的延伸率 条件(T，pH，非理想性)和各种氨基酸取代。 带有额外氨基酸突变的镰状血红蛋白突变将主要是 由洛克菲勒大学的詹姆斯·曼宁博士提供，血红蛋白 将由哥伦比亚大学的Frank Costantini博士提供 大学。 这些数据将用于测试和改进新的结构模型 在此提出的非均相成核。数据还将 允许将非均相成核的描述扩展到描述 在氧气、胎儿Hb或其他非聚合条件下的凝胶化 物种。这项工作最终将提供一幅充满活力的地图 形成坚硬的血管闭塞凝胶的相互作用。