Abstract:
An improved red blood cell (RBC) membrane model is developed based on the bilayer coupling model (BCM) to accurately predict the complete sequence of stomatocyte-discocyte-echinocyte (SDE) transformation of a RBC. The coarse-grained (CG)-RBC membrane model is proposed to predict the minimum energy configuration of the RBC from the competition between lipid-bilayer bending resistance and cytoskeletal shear resistance under given reference constraints. In addition to the conventional membrane surface area, cell volume and bilayer-leaflet-area-difference constraints, a new constraint: total-membrane-curvature is proposed in the model to better predict RBC shapes in agreement with experimental observations. A quantitative evaluation of several cellular measurements including length, thickness and shape factor, is performed for the first time, between CG-RBC model predicted and three-dimensional (3D) confocal microscopy imaging generated RBC shapes at equivalent reference constraints. The validated CG-RBC membrane model is then employed to investigate the effect of reduced cell volume and elastic length scale on SDE transformation, to evaluate the RBC deformability during SDE transformation, and to identify the most probable RBC cytoskeletal reference state. The CG-RBC membrane model can predict the SDE shape behaviour under diverse shape-transforming scenarios, in-vitro RBC storage, microvascular circulation and flow through microfluidic devices.
摘要:
基于双层耦合模型(BCM)开发了一种改进的红细胞(RBC)膜模型,以准确预测RBC的造口细胞-椎间盘细胞-棘突细胞(SDE)转化的完整序列。提出了粗粒(CG)-RBC膜模型,以在给定的参考约束下,通过脂质-双层弯曲阻力和细胞骨架剪切阻力之间的竞争来预测RBC的最小能量配置。除了常规的膜表面积,细胞体积和双层-小叶-面积差异约束,在模型中提出了一个新的约束:总膜曲率,以更好地预测RBC形状与实验观察结果一致。对几种细胞测量的定量评估,包括长度,厚度和形状因子,是第一次执行,在CG-RBC模型预测和三维(3D)共聚焦显微镜成像之间,在等效参考约束下生成RBC形状。然后采用验证的CG-RBC膜模型来研究细胞体积减少和弹性长度尺度对SDE转化的影响。为了评估SDE转化过程中的红细胞变形能力,并确定最可能的红细胞细胞骨架参考状态。CG-RBC膜模型可以预测不同形状转换场景下的SDE形状行为,体外红细胞储存,微血管循环和流过微流体装置。