Microcirculatory obstruction is a hallmark of severe malaria, but mechanisms of parasite sequestration are only partially understood. Here, we developed a robust three-dimensional microvessel model that mimics the arteriole-capillary-venule (ACV) transition consisting of a narrow 5- to 10-μm-diameter capillary region flanked by arteriole- or venule-sized vessels. Using this platform, we investigated red blood cell (RBC) transit at the single cell and at physiological hematocrits. We showed normal RBCs deformed via in vivo-like stretching and tumbling with negligible interactions with the vessel wall. By comparison, Plasmodium falciparum-infected RBCs exhibited virtually no deformation and rapidly accumulated in the capillary-sized region. Comparison of wild-type parasites to those lacking either cytoadhesion ligands or membrane-stiffening knobs showed highly distinctive spatial and temporal kinetics of accumulation, linked to velocity transition in ACVs. Our findings shed light on mechanisms of microcirculatory obstruction in malaria and establish a new platform to study hematologic and microvascular diseases.

中文翻译：

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工程人体毛细血管中感染疟疾的红细胞的生物物理和生物分子相互作用。

微循环阻塞是严重疟疾的一个标志，但寄生虫隔离的机制尚不完全清楚。在这里，我们开发了一个强大的三维微血管模型，模拟小动脉-毛细血管-小静脉 (ACV) 过渡，由狭窄的 5 至 10 μm 直径毛细血管区域组成，两侧是小动脉或小静脉大小的血管。使用该平台，我们研究了红细胞 (RBC) 在单细胞和生理血细胞比容下的转运。我们发现正常红细胞通过类似体内的拉伸和翻滚而变形，与血管壁的相互作用可以忽略不计。相比之下，恶性疟原虫感染的红细胞几乎没有表现出变形，并在毛细血管大小的区域迅速积累。野生型寄生虫与缺乏细胞粘附配体或膜硬化旋钮的寄生虫的比较显示出高度独特的空间和时间积累动力学，与ACV中的速度转变有关。我们的研究结果揭示了疟疾微循环阻塞的机制，并建立了研究血液和微血管疾病的新平台。