Fai Thomas G, Leo-Macias Alejandra, Stokes David L, Peskin Charles S
John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States of America.
Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, New York, United States of America.
PLoS Comput Biol. 2017 Oct 9;13(10):e1005790. doi: 10.1371/journal.pcbi.1005790. eCollection 2017 Oct.
We simulate deformable red blood cells in the microcirculation using the immersed boundary method with a cytoskeletal model that incorporates structural details revealed by tomographic images. The elasticity of red blood cells is known to be supplied by both their lipid bilayer membranes, which resist bending and local changes in area, and their cytoskeletons, which resist in-plane shear. The cytoskeleton consists of spectrin tetramers that are tethered to the lipid bilayer by ankyrin and by actin-based junctional complexes. We model the cytoskeleton as a random geometric graph, with nodes corresponding to junctional complexes and with edges corresponding to spectrin tetramers such that the edge lengths are given by the end-to-end distances between nodes. The statistical properties of this graph are based on distributions gathered from three-dimensional tomographic images of the cytoskeleton by a segmentation algorithm. We show that the elastic response of our model cytoskeleton, in which the spectrin polymers are treated as entropic springs, is in good agreement with the experimentally measured shear modulus. By simulating red blood cells in flow with the immersed boundary method, we compare this discrete cytoskeletal model to an existing continuum model and predict the extent to which dynamic spectrin network connectivity can protect against failure in the case of a red cell subjected to an applied strain. The methods presented here could form the basis of disease- and patient-specific computational studies of hereditary diseases affecting the red cell cytoskeleton.
我们使用浸入边界方法和细胞骨架模型来模拟微循环中的可变形红细胞,该细胞骨架模型纳入了断层图像揭示的结构细节。已知红细胞的弹性由其脂质双分子层膜和细胞骨架共同提供,脂质双分子层膜抵抗弯曲和面积的局部变化,细胞骨架抵抗面内剪切。细胞骨架由血影蛋白四聚体组成,这些四聚体通过锚蛋白和基于肌动蛋白的连接复合物与脂质双分子层相连。我们将细胞骨架建模为一个随机几何图,节点对应于连接复合物,边对应于血影蛋白四聚体,使得边长由节点之间的端到端距离给出。该图的统计特性基于通过分割算法从细胞骨架的三维断层图像中收集的分布。我们表明,在我们的模型细胞骨架中,血影蛋白聚合物被视为熵弹簧,其弹性响应与实验测量的剪切模量高度一致。通过使用浸入边界方法模拟流动中的红细胞,我们将这种离散的细胞骨架模型与现有的连续介质模型进行比较,并预测在红细胞受到外加应变的情况下,动态血影蛋白网络连通性能够防止细胞破裂的程度。本文提出的方法可以作为对影响红细胞细胞骨架的遗传性疾病进行疾病和患者特异性计算研究的基础。