Molecular insights into the irreversible mechanical behavior of sickle hemoglobin.
Molecular insights into the irreversible mechanical behavior of sickle hemoglobin.
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DOI：
10.1080/07391102.2018.1456362
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发表时间：
2019-03
影响因子：
4.4
通讯作者：
Averett RD
中科院分区：
文献类型：
--
作者：
Yesudasan S;Douglas SA;Platt MO;Wang X;Averett RD
镰状细胞病是由谷氨酸被缬氨酸取代的氨基酸引起的，这导致脱氧镰状血红蛋白（HbS）聚合成长链。这些链负责红细胞（RBC）的镰状化，使血液高凝，导致血管闭塞危机的机会增加。镰状红细胞在高粘性流体中穿过狭窄血管时的构象变化对于理解至关重要;然而，很少有研究调查镰状红细胞分子力学行为的起源。在这项工作中，我们研究了HbS分子的分子力学性质。使用力学模型来估计HbS分子的方向刚度，并将结果与成人血红蛋白（HbA）进行比较。比较显示HbS和HbA之间的强度的显著差异，以及血红蛋白分子的各向异性行为。结果还表明，HbS分子在压缩下经历比HbA更多的不可逆力学行为。此外，我们已经表征了使用六个HbS分子的双股镰刀形纤维的弹性和压缩性质，并且它表明HbS分子通过强的分子间力彼此结合。
Sickle cell disease is caused by the amino acid substitution of glutamic acid to valine, which leads to the polymerization of deoxygenated sickle hemoglobin (HbS) into long strands. These strands are responsible for the sickling of red blood cells (RBCs), making blood hyper-coagulable leading to an increased chance of vaso-occlusive crisis. The conformational changes in sickled RBCs traveling through narrow blood vessels in a highly viscous fluid are critical in understanding; however, there are few studies that investigate the origins of the molecular mechanical behavior of sickled RBCs. In this work, we investigate the molecular mechanical properties of HbS molecules. A mechanical model was used to estimate the directional stiffness of an HbS molecule and the results were compared to adult human hemoglobin (HbA). The comparison shows a significant difference in strength between HbS and HbA, as well as anisotropic behavior of the hemoglobin molecules. The results also indicated that the HbS molecule experienced more irreversible mechanical behavior than HbA under compression. Further, we have characterized the elastic and compressive properties of a double stranded sickle fiber using six HbS molecules, and it shows that the HbS molecules are bound to each other through strong inter-molecular forces.
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影响因子：
4.1
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通讯作者：
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