Pan Weichun, Galkin Oleg, Filobelo Luis, Nagel Ronald L, Vekilov Peter G
Department of Chemical Engineering, University of Houston, Houston, Texas 77204-4004, USA.
Biophys J. 2007 Jan 1;92(1):267-77. doi: 10.1529/biophysj.106.094854. Epub 2006 Oct 13.
Sickle cell hemoglobin (HbS) is a mutant, whose polymerization while in deoxy state in the venous circulation underlies the debilitating sickle cell anemia. It has been suggested that the nucleation of the HbS polymers occurs within clusters of dense liquid, existing in HbS solutions. We use dynamic light scattering with solutions of deoxy-HbS, and, for comparison, of oxy-HbS and oxy-normal adult hemoglobin, HbA. We show that solutions of all three Hb variants contain clusters of dense liquid, several hundred nanometers in size, which are metastable with respect to the Hb solutions. The clusters form within a few seconds after solution preparation and their sizes and numbers remain relatively steady for up to 3 h. The lower bound of the cluster lifetime is 15 ms. The clusters exist in broad temperature and Hb concentration ranges, and occupy 10(-5)-10(-2) of the solution volume. The results on the cluster properties can serve as test data for a potential future microscopic theory of cluster stability and kinetics. More importantly, if the clusters are a part of the nucleation mechanism of HbS polymers, the rate of HbS polymerization can be controlled by varying the cluster properties.
镰状细胞血红蛋白（HbS）是一种突变体，其在静脉循环中处于脱氧状态时发生聚合，这是导致使人衰弱的镰状细胞贫血的根本原因。有人提出，HbS聚合物的成核发生在HbS溶液中存在的致密液体簇内。我们使用动态光散射研究脱氧-HbS溶液，以及作为对照的氧合-HbS和氧合正常成人血红蛋白HbA溶液。我们发现，所有这三种血红蛋白变体的溶液都含有尺寸为几百纳米的致密液体簇，相对于血红蛋白溶液而言，这些簇是亚稳的。这些簇在溶液制备后的几秒钟内形成，其尺寸和数量在长达3小时内保持相对稳定。簇寿命的下限为15毫秒。这些簇在很宽的温度和血红蛋白浓度范围内存在，占据溶液体积的10^(-5)-10^(-2)。关于簇性质的结果可以作为未来潜在的簇稳定性和动力学微观理论的测试数据。更重要的是，如果这些簇是HbS聚合物成核机制的一部分，那么可以通过改变簇的性质来控制HbS聚合的速率。
