Mesoscopic Adaptive Resolution Scheme toward Understanding of Interactions between Sickle Cell Fibers.
Mesoscopic Adaptive Resolution Scheme toward Understanding of Interactions between Sickle Cell Fibers.
复制标题
用于理解镰状细胞纤维之间相互作用的介观自适应分辨率方案。
DOI：
10.1016/j.bpj.2017.05.050
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发表时间：
2017
影响因子：
3.4
通讯作者：
Karniadakis,GeorgeEm
中科院分区：
文献类型：
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作者：
Lu,Lu;Li,He;Bian,Xin;Li,Xuejin;Karniadakis,GeorgeEm
了解镰状血红蛋白(HBS)的细胞内聚合以及随后与红细胞膜的相互作用对于预测镰状红细胞在镰状细胞性贫血中的形态和力学性质的改变具有重要意义。然而，对HBS成核、聚合、HBS纤维相互作用以及随后的红细胞扭曲的综合过程进行建模是具有挑战性的，因为它们发生在从纳米到微米的多空间尺度上。为了在模拟集成过程方面取得进展，我们提出了一种混合HBS光纤模型，该模型通过介观自适应分辨率方案(MARS)耦合细粒度和粗粒度的HBS光纤模型。为此，我们应用微观模型来捕捉HBS纤维聚合的动态过程，同时通过介观模型保持聚合的HBS纤维的力学性能，从而为镰状细胞疾病中的亚细胞和细胞现象提供了一种桥梁。在亚细胞水平上，该模型可以模拟预先存在的HBS核的HBS聚合。在细胞水平上，如果结合RBC模型，所产生的HBS纤维可以用于研究镰刀状红细胞的形态和膜硬化。MARS的一个重要特征是，它可以很容易地用于其他基于粒子的多尺度模拟，其中需要动态粗粒化和力混合方法。作为演示，我们首先应用混合HBS纤维模型模拟了两个生长的纤维之间的相互作用，发现它们的最终构型取决于两个纤维之间的取向和相互作用距离，这与实验观察很好地一致。我们还对纤维束和结构域的形成进行了建模，以探索导致纤维分支的机制。
Understanding of intracellular polymerization of sickle hemoglobin (HbS) and subsequent interaction with the membrane of a red blood cell (RBC) is important to predict the altered morphologies and mechanical properties of sickle RBCs in sickle cell anemia. However, modeling the integrated processes of HbS nucleation, polymerization, HbS fiber interaction, and subsequent distortion of RBCs is challenging as they occur at multispatial scales, ranging from nanometers to micrometers. To make progress toward simulating the integrated processes, we propose a hybrid HbS fiber model, which couples fine-grained and coarse-grained HbS fiber models through a mesoscopic adaptive resolution scheme (MARS). To this end, we apply a microscopic model to capture the dynamic process of polymerization of HbS fibers, while maintaining the mechanical properties of polymerized HbS fibers by the mesoscopic model, thus providing a means of bridging the subcellular and cellular phenomena in sickle cell disease. At the subcellular level, this model can simulate HbS polymerization with preexisting HbS nuclei. At the cellular level, if combined with RBC models, the generated HbS fibers could be applied to study the morphologies and membrane stiffening of sickle RBCs. One important feature of the MARS is that it can be easily employed in other particle-based multiscale simulations where a dynamic coarse-graining and force-blending method is required. As demonstrations, we first apply the hybrid HbS fiber model to simulate the interactions of two growing fibers and find that their final configurations depend on the orientation and interaction distance between two fibers, in good agreement with experimental observations. We also model the formation of fiber bundles and domains so that we explore the mechanism that causes fiber branching.