Division of Applied Mathematics, Brown University, Providence, Rhode Island, USA.
Biophys J. 2012 Jan 18;102(2):185-94. doi: 10.1016/j.bpj.2011.12.006.
Sickle erythrocytes exhibit abnormal morphology and membrane mechanics under deoxygenated conditions due to the polymerization of hemoglobin S. We employed dissipative particle dynamics to extend a validated multiscale model of red blood cells (RBCs) to represent different sickle cell morphologies based on a simulated annealing procedure and experimental observations. We quantified cell distortion using asphericity and elliptical shape factors, and the results were consistent with a medical image analysis. We then studied the rheology and dynamics of sickle RBC suspensions under constant shear and in a tube. In shear flow, the transition from shear-thinning to shear-independent flow revealed a profound effect of cell membrane stiffening during deoxygenation, with granular RBC shapes leading to the greatest viscosity. In tube flow, the increase of flow resistance by granular RBCs was also greater than the resistance of blood flow with sickle-shape RBCs. However, no occlusion was observed in a straight tube under any conditions unless an adhesive dynamics model was explicitly incorporated into simulations that partially trapped sickle RBCs, which led to full occlusion in some cases.
镰状红细胞在缺氧条件下表现出异常的形态和膜力学特性,这是由于血红蛋白 S 的聚合。我们采用耗散粒子动力学(DPD)方法,通过模拟退火程序和实验观察,将经过验证的红细胞(RBC)多尺度模型扩展到可以代表不同镰状细胞形态的模型。我们使用各向异性和椭圆形状因子来量化细胞变形,结果与医学图像分析一致。然后,我们研究了在恒剪切和管流条件下镰状 RBC 悬浮液的流变性和动力学。在剪切流中,从剪切稀化到剪切独立流动的转变揭示了细胞膜僵硬在缺氧过程中的深刻影响,颗粒状 RBC 形状导致粘度最大。在管流中,颗粒状 RBC 增加的流动阻力也大于镰状 RBC 血流的阻力。然而,在任何情况下,直管中都没有观察到阻塞,除非在模拟中明确纳入粘性动力学模型,该模型部分捕获镰状 RBC,从而导致在某些情况下完全阻塞。