Fibrinogen is regarded as the main glycoprotein in the aggregation of red blood cells (RBCs), a normally occurring phenomenon that has a major impact on blood rheology and hemodynamics, especially under pathological conditions, including type 2 diabetes mellitus (T2DM). In this study, we investigate the fibrinogen-dependent aggregation dynamics of T2DM RBCs through patient-specific predictive computational simulations that invoke key parameters derived from microfluidic experiments. We first calibrate our model parameters at the doublet (a rouleau consisting of two aggregated RBCs) level for healthy blood samples by matching the detaching force required to fully separate RBC doublets with measurements using atomic force microscopy and optical tweezers. Using results from companion microfluidic experiments that also provide in vitro quantitative information on cell-cell adhesive dynamics, we then quantify the rouleau dissociation dynamics at the doublet and multiplet (a rouleau consisting of three or more aggregated RBCs) levels for obese patients with or without T2DM. Specifically, we examine the rouleau breakup rate when it passes through microgates at doublet level and investigate the effect of rouleau alignment in altering its breakup pattern at multiplet level. This study seamlessly integrates in vitro experiments and simulations and consequently enhances our understanding of the complex cell-cell interaction, highlighting the importance of the aggregation and disaggregation dynamics of RBCs in patients at increased risk of microvascular complications.

中文翻译：

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量化 2 型糖尿病中纤维蛋白原依赖性红细胞聚集


纤维蛋白原被认为是红细胞 (RBC) 聚集中的主要糖蛋白，这是一种正常发生的现象，对血液流变学和血流动力学产生重大影响，特别是在病理条件下，包括 2 型糖尿病 (T2DM)。在本研究中，我们通过调用源自微流体实验的关键参数的患者特异性预测计算模拟来研究 T2DM 红细胞的纤维蛋白原依赖性聚集动力学。我们首先通过将完全分离红细胞双联体所需的分离力与使用原子力显微镜和光镊的测量相匹配，在健康血液样本的双联体（由两个聚集的红细胞组成的轮）水平上校准我们的模型参数。利用配套微流体实验的结果（也提供细胞间粘附动力学的体外定量信息），我们对患有或不患有肥胖症患者的双峰和多重峰（由三个或更多聚集的红细胞组成的轮盘）水平的肉卷解离动力学进行量化T2DM。具体来说，我们检查了当卷绕在双峰水平上通过微门时的破碎率，并研究了卷绕排列在改变其在多重水平上的破碎模式中的效果。这项研究无缝地整合了体外实验和模拟，从而增强了我们对复杂的细胞间相互作用的理解，强调了红细胞聚集和解聚动力学对于微血管并发症风险增加的患者的重要性。