a School of Chemical, Materials, and Biomedical Engineering , University of Georgia , Athens , GA 30602 , USA.
b Wallace H. Coulter Department of Biomedical Engineering , Georgia Institute of Technology , Atlanta , GA 30332 , USA.
J Biomol Struct Dyn. 2019 Mar;37(5):1270-1281. doi: 10.1080/07391102.2018.1456362. Epub 2018 May 4.
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.
镰状细胞病是由谷氨酸的氨基酸取代导致脱氧的镰状血红蛋白 (HbS) 聚合成长链引起的。这些链负责使红细胞 (RBC) 镰状化，使血液过度凝结，从而增加血管阻塞危机的机会。在高度粘性的流体中通过狭窄血管运输的镰状 RBC 的构象变化对于理解至关重要；然而，很少有研究调查镰状 RBC 的分子机械行为的起源。在这项工作中，我们研究了 HbS 分子的分子机械特性。使用机械模型来估计 HbS 分子的定向刚度，并且将结果与成人血红蛋白 (HbA) 进行比较。比较表明 HbS 和 HbA 之间在强度上存在显着差异，以及血红蛋白分子的各向异性行为。结果还表明，在压缩下，与 HbA 相比，HSB 分子经历了更多的不可逆机械行为。此外，我们使用六个 HbS 分子表征了双链镰状纤维的弹性和压缩特性，表明 HbS 分子通过强分子间力相互结合。
