发表机构
Brown University; Massachusetts Institute of Technology; University of Georgia（布朗大学; 麻省理工学院; 佐治亚大学）
机构由 AI 辅助整理，请以论文原文为准。AI 中文总结
研究健康与疾病状态下网织红细胞生物力学，结合微流控实验与DPD模拟，发现富含网织红细胞样本有三种亚型，单细胞模拟显示微通道放大机械异质性，成对模拟揭示领先细胞对跟随细胞的影响，还明确控制变量及相关病症在机械轴上的情况。
AI 中文摘要
红细胞群体在力学上是异质的，但在受限环境中这种异质性如何影响运输、堵塞和流变学仍不清楚。我们将微流控微通道实验与耗散粒子动力学模拟相结合，研究网织红细胞形态、变形性和细胞间流体动力耦合如何控制微受限血流，并将其与急慢性高山病联系起来。富含网织红细胞的样本显示出三种亚型，通过拟合微通道通过时间和流动下形状数据进行参数化。单细胞模拟表明，5微米微通道会放大机械异质性，而弯曲主导的脾缝对亚型的区分仅为10%-20%。成对模拟表明，领先细胞不会让跟随细胞通过其自身的单细胞阈值，因此不存在数量级的尾流“解堵塞”减少，但领先细胞的顺应性会影响拥挤的单列通过：柔软的网织红细胞领先细胞会使尾随的僵硬细胞的临界通过压力相对于僵硬的（镰状特征）领先细胞降低约12%，并使其通过速度加快约10%。控制变量是单细胞临界压力梯度ΔP_c，它随着膜刚度从对照圆盘状细胞通过网织红细胞到镰状细胞特征细胞单调增加。我们的模拟再现了对照血液的剪切变稀粘度，报告的慢性高山病高粘度主要反映了血细胞比容驱动的拥挤，而不是单细胞流变学的变化。这些结果将良性适应、慢性高山病高粘度和镰状细胞特征脾综合征置于由相对于脾脏工作压力的ΔP_c定义的单一机械轴上。
英文摘要
Red blood cell (RBC) populations are mechanically and morphologically heterogeneous, yet how this heterogeneity governs transport, splenic retention and blood rheology in confinement remains unclear. We combine microchannel experiments with dissipative particle dynamics (DPD) simulations to determine how the morphology, deformability and hydrodynamic interaction of immature RBCs (reticulocytes) shape microconfined flow in acute and chronic mountain sickness. Reticulocyte-rich samples present the three shapes that the maturation literature assigns to successive reticulocyte stages -- multilobular, cup-shaped and near-discocytic -- which we model as R1-R3, each with a membrane shear modulus within the range reported for reticulocytes. A 5-um microchannel resolves these models only weakly, R1 taking at most ~18% longer than control discocytes to cross it, whereas a 1.5-um splenic slit, driven at its own loading, delays R1 by ~30%; both geometries order the models by shear modulus. In cell pairs, a leading cell never lets a follower pass below its own single-cell threshold, ruling out the order-of-magnitude reduction that a wake-"unjamming" picture would suggest; instead the follower queues behind the leader, and a stiffer leader, which clears the slit more slowly, delays it more. The controlling variable is the single-cell critical pressure gradient Delta P_c, which rises monotonically from control discocytes through the reticulocyte subtypes to sickled cells. Set against published rheograms, an analytical estimate attributes chronic-mountain-sickness hyperviscosity mainly to hematocrit-driven crowding rather than single-cell rheology. These results place benign acclimatization, chronic-mountain-sickness hyperviscosity and sickle-cell-trait splenic syndrome on a single mechanical axis defined by Delta P_c.
Commentsv2: Confined-flow assays re-run with an explicit membrane contact term; thresholds now given as ratios to the control discocyte, not absolute pressure gradients. Adds Fig 2 (new-methylene-blue staining) and Fig 7 (critical-driving ladder); collective-clogging panels removed, so v1 Figs 2-5 are now Figs 3-6 (Figs 8-9 unchanged). Methods, SI and references updated. Conclusions unchanged
