PDF(Pubmed)
Abstract：
Red blood cells (RBCs) clump together under low flow conditions in a process called RBC aggregation, which can alter RBC perfusion in a microvascular network. As elevated RBC aggregation is commonly associated with cardiovascular and inflammatory diseases, a better understanding of aggregation is essential. Unlike RBC aggregation in polymer solutions which can be well explained by polymer depletion theory, plasma-mediated RBC aggregation has features that best match explanations with cross-bridging mechanisms. Previous studies have demonstrated the dominant role of fibrinogen (Fg) in promoting aggregate formation and recent cell-force spectroscopy (CFS) experiments on interacting RBC doublets in plasma have reported an inverse relationship between disaggregation force and the adhesive contact area between RBCs. This has led investigators to revisit the hypothesis of inter-RBC cross-bridging which involves cross-bridge migration under interfacial tension during the forced disaggregation of RBC aggregates. In this study, we developed the cross-bridge migration model (CBMM) in plasma that mechanistically represents the migrating cross-bridge hypothesis. Transport of mobile Fg cross-bridges (mFg) was calculated using a convection-diffusion transport equation with our novel introduction of convective cross-bridge drift that arises due to intercellular friction. By parametrically transforming the diffusivity of mFg in the CBMM, we were able to match experimental observations of both RBC doublet formation kinematics and RBC doublet disaggregation forces under optical tweezers tension. We found that non-specific cross-bridging promotes spontaneous growth of adhesion area between RBC doublets whereas specific cross-bridging tends to prevent adhesion area growth. Our CBMM was also able to correlate Fg concentration shifts from healthy population blood plasma to SLE (lupus) condition blood plasma with the observed increase in doublet disaggregation forces for the RBC doublets in SLE plasma.
摘要：
红细胞（RBC）在低流量条件下聚集在一起，称为红细胞聚集，这可以改变微血管网络中的红细胞灌注。由于RBC聚集升高通常与心血管和炎性疾病相关,更好地理解聚合是至关重要的。与聚合物溶液中的红细胞聚集不同，聚合物消耗理论可以很好地解释，血浆介导的RBC聚集具有与交叉桥接机制的解释最匹配的特征。先前的研究已经证明了纤维蛋白原（Fg）在促进聚集体形成中的主导作用，最近的细胞力光谱（CFS）关于血浆中相互作用的红细胞双峰的实验已经报道了解聚力与红细胞之间的粘附接触面积之间的反比关系。这导致研究人员重新审视了RBC间交叉桥接的假设，该假设涉及在RBC聚集体强制解聚期间在界面张力下的跨桥迁移。在这项研究中,我们开发了等离子体中的跨桥迁移模型（CBMM），该模型在机械上代表了迁移跨桥假设。使用对流扩散传输方程计算了移动Fg跨桥（MFg）的传输，并新颖地引入了由于细胞间摩擦而产生的对流跨桥漂移。通过参数化转换MFg在CBMM中的扩散率，在光学镊子张力下，我们能够匹配RBC双峰形成运动学和RBC双峰解聚力的实验观察结果。我们发现，非特异性交叉桥接可促进RBC双峰之间粘附区域的自发生长，而特异性交叉桥接倾向于阻止粘附区域的生长。我们的CBMM还能够将从健康人群血浆到SLE（狼疮）状况血浆的Fg浓度变化与观察到的SLE血浆中RBC双峰的双峰解聚力的增加相关联。
