Wall Shear Stress-Based Model for Adhesive Dynamics of Red Blood Cells in Malaria
Wall Shear Stress-Based Model for Adhesive Dynamics of Red Blood Cells in Malaria
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DOI：
10.1016/j.bpj.2011.03.027
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发表时间：
2011-05-04
影响因子：
3.4
通讯作者：
Karniadakis, George Em
中科院分区：
文献类型：
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作者：
Fedosov, Dmitry A.;Caswell, Bruce;Karniadakis, George Em
恶性疟原虫(PF-RBCs)感染的红细胞(RBC)失去了膜的变形性，并且与血管内皮细胞和其他健康和感染的RBC的粘附性增强。这种综合作用可能会导致毛细血管闭塞导致正常血液循环严重中断。在这里，我们扩展了黏附模型，利用三维、多尺度的RBC模型来研究PF-RBC的黏附动力学作为壁面切应力(WSS)和其他参数的函数。确定了几种类型的粘接行为，包括牢固的粘合、翻转动力学和沿壁缓慢滑动。特别是，在实验中观察到的PF-RBC的翻转动力学似乎是由于感染细胞的刚性增加以及RBC内固体寄生虫的存在，这可能导致不规则的黏附行为。具体地说，从爬行动力学到翻转行为的转变发生在杨氏模数大约是健康红细胞的三倍时。如果将现有键对受体和配体的作用力模拟为WSS的非线性函数，则PF-RBC的模拟动力学与现有的微流控实验具有很好的定量一致性。
Red blood cells (RBCs) infected by the Plasmodium falciparum (Pf-RBCs) parasite lose their membrane deformability and they also exhibit enhanced cytoadherence to vascular endothelium and other healthy and infected RBCs. The combined effect may lead to severe disruptions of normal blood circulation due to capillary occlusions. Here we extend the adhesion model to investigate the adhesive dynamics of Pf-RBCs as a function of wall shear stress (WSS) and other parameters using a three-dimensional, multiscale RBC model. Several types of adhesive behavior are identified, including firm adhesion, flipping dynamics, and slow slipping along the wall. In particular, the flipping dynamics of Pf-RBCs observed in experiments appears to be due to the increased stiffness of infected cells and the presence of the solid parasite inside the RBC, which may cause an irregular adhesion behavior. Specifically, a transition from crawling dynamics to flipping behavior occurs at a Young's modulus approximately three times larger than that of healthy RBCs. The simulated dynamics of Pf-RBCs is in excellent quantitative agreement with available microfluidic experiments if the force exerted on the receptors and ligands by an existing bond is modeled as a nonlinear function of WSS.