高雪病患者红细胞生物物理特性的量化研究
Quantifying the Biophysical Properties of Red Blood Cells in Gaucher Disease
AI总结：
本研究结合计算与实验，量化高雪病患者红细胞的剪切模量、表面积体积比等关键生物物理参数，构建三种亚型并揭示其对红细胞异常行为及血液粘度的影响，为关联细胞特性与病理提供了框架。
AI中文摘要：
高雪病（Gaucher disease, GD）是最常见的溶酶体贮积症，会改变红细胞（red blood cell, RBC）的力学特性与循环状态，进而引发血管闭塞、骨梗死及脾肿大等症状。然而，GD患者红细胞（GD-RBC）的生物物理特性在这些病理过程中的单独作用尚不明确。本研究采用计算与实验结合的方法，对GD-RBC的生物物理特性进行定量表征，并明确特定力学参数如何驱动红细胞的异常行为。基于实验数据，我们独立量化了红细胞的关键特性，包括剪切模量（μ）、表面积体积比（S/V）和弯曲模量（k_c）。基于这些参数，我们构建了三种GD-RBC亚型（GD-RBC1-3），以系统分离各参数的单独贡献。在单细胞层面，光镊模拟显示，轴向直径减少约27%，横向压缩量减少约42%；坦克履带式运动呈现非单调特性，在弯曲刚度升高时，旋转频率可增加最多约70%或降低。在受限流动中，红细胞通过微通道狭窄处的时间增加一倍以上，而严重GD-RBC亚型通过脾裂隙的时间从对照组的约250毫秒升至1200毫秒以上，接近功能上的无法通过阈值。在群体层面，粘度模拟表明，这些改变共同升高了血液粘度，其中小比例（约4.0%）的高刚性细胞会不成比例地增加流动阻力。总体而言，本研究提供了一个定量且机械性的框架，可分离关键红细胞参数对GD异常行为的贡献，将细胞尺度的生物物理特性与血液功能障碍及微血管闭塞联系起来。
英文摘要：
Gaucher disease (GD), the most common lysosomal storage disorder, alters red blood cell (RBC) mechanics and circulation, contributing to vascular occlusions, bone infarcts, and splenomegaly. However, the individual roles of GD-RBC biophysical properties in these processes remain unclear. Here, we present a combined computational-experimental investigation to quantitatively characterize GD-RBC biophysical properties and determine how specific mechanical parameters drive abnormal RBC behavior. Informed by experimental data, we independently quantify key RBC properties, including shear modulus (mu), surface-to-volume ratio (S/V), and bending modulus (k_c). Based on these parameters, we construct three GD-RBC subtypes (GD-RBC1-3) to systematically isolate their individual contributions. At the single-cell level, optical tweezers simulations show up to ~27% reduction in axial diameter and ~42% reduction in transverse compression. Tank-treading dynamics exhibit non-monotonic behavior, with rotation frequencies increasing by up to ~70% or decreasing under elevated bending rigidity. In confined flow, traversal times through microchannel constrictions increase by more than a factor of two, while splenic slit passage times rise from ~250 ms (control) to >1200 ms for the severe GD-RBC subtype, approaching a functional no-passage threshold. At the population level, viscosity simulations demonstrate that these alterations collectively elevate blood viscosity, with small fractions (~4.0%) of highly rigid cells disproportionately increasing flow resistance. Overall, this study provides a quantitative and mechanistic framework that disentangles the contributions of key RBC parameters to abnormal behavior in GD, linking cellular-scale biophysics to hematologic dysfunction and microvascular occlusion.
