通过模拟与微流控结合，揭示了红细胞形态与力学特性如何决定遗传性口形红细胞症的治疗效果差异。
Quantifying the biophysical properties of stomatocytes in health and disease
- 构建四类红细胞模型，系统模拟从过度水化到脱水的形态变化。
- 发现脱水型口形红细胞易通过血管缝隙但显著增加血液黏度约29%。
- 开发无标记芯片可区分四种红细胞类型，适用于术前风险评估。
遗传性口形红细胞症（HS）是一组以杯状红细胞为特征的疾病，其对脾切除术的反应截然相反：过度水化型（OHS）可治愈，而脱水型（DHS/ xerocytosis）可能引发血栓。这一矛盾源于红细胞生物力学受剪切模量、弯曲刚度、表面积体积比（S/V）和胞质黏度等独立参数控制，现有检测手段仅能部分捕捉。本研究结合耗散粒子动力学（DPD）模拟与微流控成像，构建了固定膜面积下体积递减（109.7、101.5、89.8 fL）的四种红细胞模型（健康盘状及三类口形红细胞，ST-RBC1-3），跨越OHS至DHS范围。通过五种力学正交测试发现，跨内皮缝隙（IES）通过主要由几何决定：过度水化型ST-RBC1所需临界压力较正常红细胞高一个数量级，而脱水型ST-RBC3可自由通过。然而ST-RBC3抑制膜旋转并使低剪切全血黏度在生理血细胞比容下升高约29%，接近戈谢病引起的高黏血症水平。一种漏斗障碍芯片将这些差异放大为无标记的中心线偏移信号，预测可区分所有四类红细胞（极端表型间差异达4.5个标准差）。该结果统一了单细胞力学、脾脏过滤与血液流变学，破解了脾切除矛盾，并指向微流控技术用于HS术前风险分层。
原文摘要 · Abstract (English)
Hereditary stomatocytosis (HS) comprises red blood cell (RBC) disorders characterized by cup-shaped erythrocytes that respond oppositely to splenectomy: curative in overhydrated HS (OHS) but potentially thrombogenic in dehydrated HS (DHS/xerocytosis). This paradox persists because RBC biomechanics is governed by partly independent parameters--shear modulus, bending rigidity, surface-to-volume ratio (S/V), and cytoplasmic viscosity--that existing assays capture only piecemeal. Here we combine dissipative particle dynamics (DPD) simulations with microfluidic imaging to construct a control discocyte and three stomatocyte models (ST-RBC1-3) at fixed membrane area and decreasing volume (109.7, 101.5, 89.8 fL), spanning the OHS-to-DHS range. Tracing this parameter set through five mechanically orthogonal assays, we find that interendothelial-slit (IES) traversal is geometry-dominated: overhydrated ST-RBC1 requires an order of magnitude higher critical pressure than healthy RBCs, whereas dehydrated ST-RBC3 passes freely. ST-RBC3 nonetheless suppresses membrane tank-treading and raises low-shear whole-blood viscosity by ~29% at physiological haematocrit, comparable to Gaucher-disease hyperviscosity. A funnel-obstacle chip amplifies these differences into a label-free centerline-offset signal predicted to separate all four RBC types (~4.5 standard deviations between extreme phenotypes). These results unite single-cell mechanics, splenic filtration, and hemorheology in one framework, resolve the splenectomy paradox, and point toward microfluidic pre-operative risk stratification in HS.
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