High-throughput quantification of red blood cell deformability and oxygen saturation to probe mechanisms of sickle cell disease.
High-throughput quantification of red blood cell deformability and oxygen saturation to probe mechanisms of sickle cell disease.
复制标题
对红细胞变形性和氧饱和度进行高通量定量，以探讨镰状细胞病的机制。
DOI：
10.1073/pnas.2313755120
复制
发表时间：
2023
影响因子：
11.1
通讯作者：
Wood,DavidK
中科院分区：
文献类型：
--
作者：
Williams,DillonC;Wood,DavidK
镰状细胞病复杂的全身性病理是由多种机制驱动的，包括红细胞（rbc）被脱氧镰状血红蛋白聚合纤维硬化。了解含聚合物红细胞的病理作用的关键一步是量化这些细胞在生理上相关的氧环境中的生物物理变化。我们开发了一个微流控平台，能够同时测量单个红细胞在可控氧和剪切应力下的变形能力和氧饱和度。我们发现红细胞与可检测量的聚合物有降低氧亲和力和降低变形能力。令人惊讶的是，含聚合物细胞的可变形性与氧气无关，而这些细胞的比例随着氧气的减少而增加。我们还发现这些细胞的一部分存在于大多数生理性氧紧张中，这表明这些细胞在全身性病理中起作用。此外，测量这些病理细胞的能力应该为评估治疗提供更清晰的目标。
The complex, systemic pathology of sickle cell disease is driven by multiple mechanisms including red blood cells (RBCs) stiffened by polymerized fibers of deoxygenated sickle hemoglobin. A critical step toward understanding the pathologic role of polymer-containing RBCs is quantifying the biophysical changes in these cells in physiologically relevant oxygen environments. We have developed a microfluidic platform capable of simultaneously measuring single RBC deformability and oxygen saturation under controlled oxygen and shear stress. We found that RBCs with detectable amounts of polymer have decreased oxygen affinity and decreased deformability. Surprisingly, the deformability of the polymer-containing cells is oxygen-independent, while the fraction of these cells increases as oxygen decreases. We also find that some fraction of these cells is present at most physiologic oxygen tensions, suggesting a role for these cells in the systemic pathologies. Additionally, the ability to measure these pathological cells should provide clearer targets for evaluating therapies.