Li Ju, Lykotrafitis George, Dao Ming, Suresh Subra
Department of Materials Science and Engineering, Ohio State University, Columbus, OH 43210, USA.
Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):4937-42. doi: 10.1073/pnas.0700257104. Epub 2007 Mar 12.
The human erythrocyte (red blood cell, RBC) demonstrates extraordinary ability to undergo reversible large deformation and fluidity. Such mechanical response cannot be consistently rationalized on the basis of fixed connectivity of the cell cytoskeleton that comprises the spectrin molecular network tethered to phospholipid membrane. Active topological remodeling of spectrin network has been postulated, although detailed models of such dynamic reorganization are presently unavailable. Here we present a coarse-grained cytoskeletal dynamics simulation with breakable protein associations to elucidate the roles of shear stress, specific chemical agents, and thermal fluctuations in cytoskeleton remodeling. We demonstrate a clear solid-to-fluid transition depending on the metabolic energy influx. The solid network's plastic deformation also manifests creep and yield regimes depending on the strain rate. This cytoskeletal dynamics model offers a means to resolve long-standing questions regarding the reference state used in RBC elasticity theory for determining the equilibrium shape and deformation response. In addition, the simulations offer mechanistic insights into the onset of plasticity and void percolation in cytoskeleton. These phenomena may have implication for RBC membrane loss and shape change in the context of hereditary hemolytic disorders such as spherocytosis and elliptocytosis.
人类红细胞展现出了非凡的能力，能够经历可逆的大变形和具有流动性。这种机械响应无法基于由附着在磷脂膜上的血影蛋白分子网络构成的细胞骨架的固定连接性得到一致的合理解释。尽管目前尚无此类动态重组的详细模型，但已推测出血影蛋白网络存在主动的拓扑重塑。在此，我们提出一种具有可断裂蛋白质关联的粗粒度细胞骨架动力学模拟，以阐明剪切应力、特定化学试剂和热涨落在细胞骨架重塑中的作用。我们证明了根据代谢能量流入情况会出现明显的固 - 液转变。固体网络的塑性变形还会根据应变率表现出蠕变和屈服状态。这种细胞骨架动力学模型提供了一种方法，可解决红细胞弹性理论中用于确定平衡形状和变形响应的参考状态相关的长期问题。此外，这些模拟为细胞骨架中可塑性的起始和空隙渗流提供了机制性见解。在遗传性溶血性疾病（如球形红细胞增多症和椭圆形红细胞增多症）的背景下，这些现象可能与红细胞膜的损失和形状变化有关。
