Metastable mesoscopic clusters in solutions of sickle-cell hemoglobin
Metastable mesoscopic clusters in solutions of sickle-cell hemoglobin
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DOI：
10.1529/biophysj.106.094854
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发表时间：
2007-01-01
影响因子：
3.4
通讯作者：
Vekilov, Peter G.
中科院分区：
文献类型：
--
作者：
Pan, Weichun;Galkin, Oleg;Vekilov, Peter G.
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的聚合是使人衰弱的镰状细胞贫血的基础。有人提出，HbS聚合物的成核发生在存在于HbS溶液中的稠密液体的簇内。我们使用动态光散射与脱氧-HbS的解决方案，并进行比较，氧-HbS和氧正常成人血红蛋白，HbA。我们发现，所有三个血红蛋白变体的解决方案包含密集的液体，几百纳米的大小，这是相对于血红蛋白的解决方案亚稳态的集群。在溶液制备后几秒钟内形成簇，并且它们的大小和数量保持相对稳定长达3小时。团簇寿命的下限为15 ms，团簇存在于较宽的温度和Hb浓度范围内，团簇占溶液体积的10（-5）~ 10（-2）。对团簇性质的研究结果可以作为未来团簇稳定性和动力学微观理论的测试数据。更重要的是，如果簇是HbS聚合物的成核机制的一部分，则可以通过改变簇的性质来控制HbS聚合的速率。
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.