Heterogeneous Nucleation in Sickle Cell Disease

镰状细胞病中的异质成核

• 批准号: 6603787
• 负责人: FRANK A FERRONE
• 金额: $ 22.07万
• 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 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6603787
• 关键词: biophysics; capillary; erythrocytes; fluid flow; gel; hemoglobin F; hemoglobin Ss; physical model; polymerization; polymers; protein structure function; sickle cell anemia; thermodynamics; viscosity

Sickle cell disease arises because of polymerization via a double nucleation mechanism involving homogeneous nucleation in solution and heterogeneous nucleation onto sickle hemoglobin polymer surfaces. The polymers form a gel that ultimately leads to capillary occlusion. This work will continue testing the description of heterogeneous nucleation developed in the last grant period. Nucleation rates on HbF mixtures with HbS will be measured and compared with the improved theories we have now developed. We will test our structural model by studies on modified and mutant hemoglobins. (provided by Dr. Adachi and Dr. Manning) The Overall aim is to produce a structurally motivated, computationally accurate model for gelation kinetics. In the studies in the last grant period it has become apparent that vibrational freedom of molecules within the aggregate expert profound control over the rate of polymerization. We will measure nucleation rates for several mutants, which are expected to affect the vibrational entropy. Finally we will begin experiments using particle-tracking- correlation techniques to probe the microrheology of gels as a function of domain size, polymer mass, and kinetics of formation. This will address a major gap in understanding, viz. how the well-described molecular events relate to the rigidity of the polymer mass formed. Rigidity of the gels will be compared with the vibrational entropy deduced above.

镰状细胞疾病是由于聚合通过涉及溶液中均质成核和在镰状血红蛋白聚合物表面的异质成核中的两种成核机制而产生的。 聚合物形成凝胶，最终导致毛细血管阻塞。 这项工作将继续测试在上一个赠款期间开发的异质成核的描述。 将测量HBF混合物对HBF混合物的成核速率，并将其与我们现在开发的改进理论进行了比较。 我们将通过对修饰和突变血红蛋白的研究来测试我们的结构模型。 （由Adachi博士和Manning博士提供）的总体目的是为凝胶化动力学生成一个以结构动机的计算精确模型。在最后一个赠款期间的研究中，很明显，在总体专家中，分子的振动自由对聚合速率进行了深刻的控制。 我们将测量几个突变体的成核速率，这些突变体有望影响振动熵。最后，我们将使用粒子跟踪 - 相关技术开始实验，以探测凝胶的微流变学，这是域大小，聚合物质量和形成动力学的函数。 这将解决理解的主要差距，即。描述良好的分子事件与形成的聚合物质量的刚度如何相关。 将凝胶的刚度与上面推论的振动熵进行比较。