Biophysical and biomolecular interactions of malaria-infected erythrocytes in engineered human capillaries

• Published in: Science advances 2020-01, Vol.6 (3), p.eaay7243-eaay7243
• Main Authors: Arakawa, Christopher, Gunnarsson, Celina, Howard, Caitlin, Bernabeu, Maria, Phong, Kiet, Yang, Eric, DeForest, Cole A, Smith, Joseph D, Zheng, Ying
• Format: Article
• Language: English
• Subjects: Health and Medicine; Life Sciences; SciAdv r-articles
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.aay7243

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, -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.