Spectrin-level modeling of the cytoskeleton and optical tweezers stretching of the erythrocyte
Spectrin-level modeling of the cytoskeleton and optical tweezers stretching of the erythrocyte
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DOI：
10.1529/biophysj.104.047332
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发表时间：
2005-05-01
影响因子：
3.4
通讯作者：
Suresh, S
中科院分区：
文献类型：
--
作者：
Li, J;Dao, M;Suresh, S
我们提出了一个三维计算研究的全细胞平衡形状和变形的人红细胞（RBC）使用spectrin水平的能量学。随机网络模型由度为2，3，...，9结复合物和spectrin链接用于填充球形和双凹表面和中间形状，然后在spectrin连接性固定的情况下进行粗粒度分子动力学模拟。首先用胞质溶胶填充球体，并在保持其总表面积的同时逐渐放气，直到达到与真实的RBC一致的胞质溶胶体积。通过假设血影蛋白四聚体链接满足蠕虫状链自由能模型，通过能量最小化确定平衡形状。随后，模拟了初始平衡形状的光镊直接拉伸，以提取轴向直径和横向直径随拉伸力的变化。在持续长度p = 7.5 nm的spectrin四聚体分子和相应的面内剪切模量μ（0）接近8.3 μ N/m，我们的模型显示出合理的协议与最近的实验测量的大变形的红细胞与光镊。我们发现，用于面内弹性能量的参考状态的选择是决定平衡形状的关键。如果在de中使用与位置无关的材质参考状态（如完整球体），考虑到面内能量，则弯曲模量κ需要比广泛接受的2 × 10（-19）J的值大至少十倍，以相对于杯形稳定双凹面形状。我们证明，通过详细的计算，这个悖论可以避免调用的物理假设，spectrin网络进行不断的重塑总是放松面内剪切弹性能为零，在任何宏观形状，在一些缓慢的特征时间尺度。我们已经设计并实现了一个液化网络结构进化算法，放松剪切应力无处不在的网络，并产生细胞骨架结构，模仿实验观察。
We present a three-dimensional computational study of whole-cell equilibrium shape and deformation of human red blood cell (RBC) using spectrin-level energetics. Random network models consisting of degree-2, 3,..., 9 junction complexes and spectrin links are used to populate spherical and biconcave surfaces and intermediate shapes, and coarse-grained molecular dynamics simulations are then performed with spectrin connectivities fixed. A sphere is first filled with cytosol and gradually deflated while preserving its total surface area, until cytosol volume consistent with the real RBC is reached. The equilibrium shape is determined through energy minimization by assuming that the spectrin tetramer links satisfy the worm-like chain free-energy model. Subsequently, direct stretching by optical tweezers of the initial equilibrium shape is simulated to extract the variation of axial and transverse diameters with the stretch force. At persistence length p = 7.5 nm for the spectrin tetramer molecule and corresponding in-plane shear modulus mu(0) approximate to 8.3 mu N/m, our models show reasonable agreement with recent experimental measurements on the large deformation of RBC with optical tweezers. We find that the choice of the reference state used for the in-plane elastic energy is critical for determining the equilibrium shape. If a position-independent material reference state such as a full sphere is used in de. ning the in-plane energy, then the bending modulus kappa needs to be at least a decade larger than the widely accepted value of 2 x 10(-19) J to stabilize the biconcave shape against the cup shape. We demonstrate through detailed computations that this paradox can be avoided by invoking the physical hypothesis that the spectrin network undergoes constant remodeling to always relax the in-plane shear elastic energy to zero at any macroscopic shape, at some slow characteristic timescale. We have devised and implemented a liquefied network structure evolution algorithm that relaxes shear stress everywhere in the network and generates cytoskeleton structures that mimic experimental observations.