Physical mechanisms of red blood cell splenic filtration
Physical mechanisms of red blood cell splenic filtration
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DOI：
10.1073/pnas.2300095120
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发表时间：
2023-10-31
影响因子：
11.1
通讯作者：
Peng, Zhangli
中科院分区：
文献类型：
--
作者：
Moreau, Alexis;Yaya, Francois;Peng, Zhangli
脾内皮间缝的基本功能是不断过滤血液中的红细胞（rbc），以消除异常和老化的细胞。迄今为止，8克红细胞通过0.3克宽的狭缝的过程仍然是个谜。在红细胞通过过程中狭缝口径是否如有时所建议的那样增大？在这里，我们通过结合多尺度建模、实时成像和微流控实验，阐明了控制红细胞在狭缝中保留或通过动力学的机制，该设备具有亚微米宽的生理校准狭缝。我们观察到健康的红细胞在37摄氏度时通过0.28克宽的刚性狭缝。要实现这一壮举，他们必须满足两个条件。在几何上，它们的表面积体积比必须与两个系绳连接的相等球体的形状相容。机械地说，具有低表面积体积比的细胞（在0.4克宽的狭缝中有28%的红细胞）必须在狭缝内局部展开它们的光谱细胞骨架。相反，机械敏感的PIEZO1通道的激活是不需要的。RBC通过狭缝的时间随狭缝内压降和滑移宽度分别呈-1和-3次幂律。这个定律类似于二维泊泽维尔流中的牛顿流体，表明红细胞的动力学是由它们的细胞质粘度控制的。总之，我们的结果表明，通过亚微宽的狭缝过滤是可能的，而无需进一步打开狭缝。此外，我们的方法解决了对用于输血和药物输送的病变红细胞或工程红细胞的脾清除体外评估的关键需求。
The splenic interendothelial slits fulfill the essential function of continuously filtering red blood cells (RBCs) from the bloodstream to eliminate abnormal and aged cells. To date, the process by which 8 gm RBCs pass through 0.3 gm-wide slits remains enigmatic. Does the slit caliber increase during RBC passage as sometimes suggested? Here, we elucidated the mechanisms that govern the RBC retention or passage dynamics in slits by combining multiscale modeling, live imaging, and microfluidic experiments on an original device with submicron-wide physiologically calibrated slits. We observed that healthy RBCs pass through 0.28 gm-wide rigid slits at 37 C-degrees. To achieve this feat, they must meet two requirements. Geometrically, their surface area-to-volume ratio must be compatible with a shape in two tether-connected equal spheres. Mechanically, the cells with a low surface area-to-volume ratio (28% of RBCs in a 0.4 gm-wide slit) must locally unfold their spectrin cytoskeleton inside the slit. In contrast, activation of the mechanosensitive PIEZO1 channel is not required. The RBC transit time through the slits follows a -1 and -3 power law with in-slit pressure drop and slip width, respectively. This law is similar to that of a Newtonian fluid in a twodimensional Poiseuille flow, showing that the dynamics of RBCs is controlled by their cytoplasmic viscosity. Altogether, our results show that filtration through submicronwide slits is possible without further slit opening. Furthermore, our approach addresses the critical need for in vitro evaluation of splenic clearance of diseased or engineered RBCs for transfusion and drug delivery.