STRUCTURE AND INTERACTION IN SICKLE HEMOGLOBIN GELS

镰状血红蛋白凝胶的结构和相互作用

• 批准号: 6922085
• 负责人: ROBIN Walt BRIEHL
• 金额: $ 33.14万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6922085
• 关键词: bioenergetics; cell component structure /function; clinical research; crosslink; cytoskeleton; erythrocyte membrane; erythrocytes; gel; hemodynamics; hemoglobin Ss; human tissue; intracellular; polymerization; protein structure function; sickle cell crisis

DESCRIPTION (provided by applicant): We focus on 3 themes integral to induction, mechanisms and inhibition of pathogenesis of sickle cell crises. 1) Rheology: HbS gels are solid-like and viscoelastic. Their rheology and potential for microvascular obstruction depend on HbS fiber mechanics, which we have characterized, and fiber cross-linking. We will characterize gel elasticity, viscosity and yield strengths and relate these to fiber mechanics. We will also measure interfiber forces responsible for cross-linking. 2) Kinetics & equilibria: Gelatin kinetics are critical for pathogenesis because of the highly variable nucleation dependent delay time. We seek to identify the site of heterogeneous nucleation of new fibers on pre-existing ones and part of the delay time. The possibility that new fibers may arise from fiber defects will be studied. Contributions of component parts of delay time, including a delay that depends on the critical level of rheology, will be measured. Their mutability will be examined with the aim of inhibiting pathogenesis by increasing the delay. Energetics of the incorporation of hemoglobin A into the polymer, relevant to mutant site interactions, will be studied. 3) Depolymerization: Since depolymerization rates and mechanisms may contribute to pathology, a possibility previously little considered, we will continue to characterize this process, including the fiber elongation 'on' and 'off' rates and the mechanism and rates of the second mechanism of depolymerization we have identified, rapid depolymerization from fiber sides. Finally, we will study the rates and mechanisms of depolymerization of domains, the basic units within gels.

描述（由申请人提供）： 我们专注于3个主题，这是诱导，机制和对镰刀发病机理的抑制 细胞危机。 1）流变学：HBS凝胶具有固体状和粘弹性。他们的流变学和潜力 微血管阻塞取决于我们已经表征的HBS纤维力学，并且 纤维交联。我们将表征凝胶弹性，粘度和屈服强度，并与之相关 这些对纤维力学。我们还将测量负责交联的互动力。 2） 动力学与平衡：明胶动力学对于发病机理至关重要，因为高度可变 成核依赖性延迟时间。我们试图确定异质成核的位置 预先存在的纤维和延迟时间的一部分。新纤维可能 将研究纤维缺陷。延迟时间组件部分的贡献， 包括延迟取决于临界水平的延迟，将被衡量。他们的 将检查可突变性，目的是通过增加延迟来抑制发病机理。 将血红蛋白A掺入聚合物的能量学，与突变位点有关 互动将进行研究。 3）解聚：解聚速率和 机制可能有助于病理学，这是以前几乎没有考虑的可能性，我们将 继续表征此过程，包括纤维伸长率“ on”和“ off”率以及 我们已经确定的第二种解聚机制的机制和速率很快 纤维侧的解聚。最后，我们将研究的速率和机制 域，凝胶中的基本单元的解聚。