Predicting the morphology of sickle red blood cells using coarse-grained models of intracellular aligned hemoglobin polymers.
Predicting the morphology of sickle red blood cells using coarse-grained models of intracellular aligned hemoglobin polymers.
复制标题
DOI：
10.1039/c2sm07294g
复制
发表时间：
2012-04-28
期刊：
影响因子：
3.4
通讯作者：
Karniadakis GE
中科院分区：
文献类型：
--
作者：
Lei H;Karniadakis GE
镰状红细胞（SS-RBC）表现出异质的细胞形态（镰状、冬青叶、颗粒状等）。由于镰状血红蛋白的聚合而处于脱氧状态。实验证据表明SS-RBC形态与细胞内排列的血红蛋白聚合物之间存在密切关系。在这里，我们开发了一个粗粒度（CG）的随机模型来表示细胞内对齐的血红蛋白聚合物结构域的增长。CG模型的基础上校准的机械性能（杨氏模量，弯曲刚度）的镰状血红蛋白纤维的实验报告。细胞膜转换的过程中模拟生理对齐血红蛋白聚合物的配置和平均红细胞血红蛋白浓度。在实验中观察到的典型SS-RBC形态可以从当前模型中获得，作为细胞内对齐血红蛋白聚合物发展的结果，而无需引入任何进一步的特设假设。结果发现，SS-RBC的最终形状主要由对齐的血红蛋白聚合物结构域的角宽度决定，但它也取决于，在较小程度上，对聚合物的生长速率和细胞膜的刚性。细胞形态量化的结构形状因子，这符合医学图像的实验结果。
Sickle red blood cells (SS-RBCs) exhibit heterogeneous cell morphologies (sickle, holly leaf, granular, etc.) in the deoxygenated state due to the polymerization of the sickle hemoglobin. Experimental evidence points to a close relationship between SS-RBC morphology and intracellular aligned hemoglobin polymers. Here, we develop a coarse-grained (CG) stochastic model to represent the growth of the intracellular aligned hemoglobin polymer domain. The CG model is calibrated based on the mechanical properties (Young’s modulus, bending rigidity) of the sickle hemoglobin fibers reported in experiments. The process of the cell membrane transition is simulated for physiologic aligned hemoglobin polymer configurations and mean corpuscular hemoglobin concentration. Typical SS-RBC morphologies observed in experiments can be obtained from the current model as a result of the intracellular aligned hemoglobin polymer development without introducing any further ad hoc assumptions. It is found that the final shape of SS-RBCs is primarily determined by the angular width of the aligned hemoglobin polymer domain, but it also depends, to a lesser degree, on the polymer growth rate and the cell membrane rigidity. Cell morphologies are quantified by structural shape factors, which agree well with experimental results from medical images.