Biophysical and biomolecular interactions of malaria-infected erythrocytes in engineered human capillaries.
Sci Adv
; 6(3): eaay7243, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-32010773
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Plasmodium falciparum
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Engenharia Tecidual
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Eritrócitos
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Fenômenos Biofísicos
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Malária
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos