Vesiculation of healthy and defective red blood cells
Vesiculation of healthy and defective red blood cells
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DOI：
10.1103/physreve.92.012715
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发表时间：
2015-07-21
影响因子：
2.4
通讯作者：
Lykotrafitis, George
中科院分区：
文献类型：
--
作者：
Li, He;Lykotrafitis, George
成熟红细胞（RBC）的囊泡化有助于去除红细胞膜的缺陷补丁。在与红细胞膜蛋白质缺陷有关的血液疾病中，质膜的囊泡化被加强。已经提出了几种假说来解释红细胞囊泡形成，但确切的潜在机制和决定囊泡大小的因素仍然没有完全理解。在这项工作中，我们应用一个两个组件的粗粒度分子动力学RBC膜模型来研究如何RBC囊泡是由膜的自发曲率和膜的侧向压缩控制。我们的模拟结果表明，直径小于40 nm的小的均匀囊泡的形成可以归因于膜域的大的自发曲率。另一方面，对膜的压缩可导致形成具有不均匀组成的囊泡，其大小与细胞骨架围栏的大小相当。当同时考虑自发弯曲和侧向压缩时，膜上的压缩倾向于促进源自弯曲膜域的囊泡的形成。我们还模拟红细胞膜缺陷连接到遗传性椭圆形红细胞增多症（HE）和遗传性球形红细胞增多症（HS）的囊泡形成。当脂质双层和膜骨架之间的垂直连接性升高时，如在正常RBC中，多个囊泡从压缩的膜脱落，其直径与细胞骨架畜栏大小相似。在HS RBC中，脂质双层和细胞骨架之间的连接性降低，在与正常RBC相同的压缩比下释放较大尺寸的囊泡。最后，我们发现从HE RBC释放的囊泡可以包含由于膜骨架的碎片化而从HS RBC释放的囊泡的细胞骨架丝耗尽。
Vesiculation of mature red blood cells (RBCs) contributes to removal of defective patches of the erythrocyte membrane. In blood disorders, which are related to defects in proteins of the RBC membrane, vesiculation of the plasma membrane is intensified. Several hypotheses have been proposed to explain RBC vesiculation but the exact underlying mechanisms and what determines the sizes of the vesicles are still not completely understood. In this work, we apply a two-component coarse-grained molecular dynamics RBC membrane model to study how RBC vesiculation is controlled by the membrane spontaneous curvature and by lateral compression of the membrane. Our simulation results show that the formation of small homogeneous vesicles with a diameter less than 40 nm can be attributed to a large spontaneous curvature of membrane domains. On the other hand, compression on themembrane can cause the formation of vesicles with heterogeneous composition and with sizes comparable with the size of the cytoskeleton corral. When spontaneous curvature and lateral compression are simultaneously considered, the compression on the membrane tends to facilitate formation of vesicles originating from curved membrane domains. We also simulate vesiculation of RBCs with membrane defects connected to hereditary elliptocytosis (HE) and to hereditary spherocytosis (HS). When the vertical connectivity between the lipid bilayer and the membrane skeleton is elevated, as in normal RBCs, multiple vesicles are shed from the compressed membrane with diameters similar to the cytoskeleton corral size. In HS RBCs, where the connectivity between the lipid bilayer and the cytoskeleton is reduced, larger-size vesicles are released under the same compression ratio as in normal RBCs. Lastly, we find that vesicles released from HE RBCs can contain cytoskeletal filaments due to fragmentation of the membrane skeleton while vesicles released from the HS RBCs are depleted of cytoskeletal filaments.