A microfluidic model for single-cell capillary obstruction by Plasmodium falciparum -infected erythrocytes
Year: 2003
Type: article
Abstract: Severe malaria by Plasmodium falciparum is a potentially fatal disease, frequently unresponsive to even the most aggressive treatments. Host organ failure is associated with acquired rigidity of infected red blood cells and capillary blockage. In vitro techniques have played an important role in modeling cell deformability. Although, historically they have either been applied to bulk cell populations or to measure single physical parameters of individual cells. In this article, we demonstrate the unique abilities and benefits of elastomeric microchannels to characterize complex behaviors of single cells, under flow, in multicellular capillary blockages. Channels of 8-, 6-, 4-, and 2-microm widths were readily traversed by the 8 microm-wide, highly elastic, uninfected red blood cells, as well as by infected cells in the early ring stages. Trophozoite stages failed to freely traverse 2- to 4-microm channels; some that passed through the 4-microm channels emerged from constricted space with deformations whose shape-recovery could be observed in real time. In 2-microm channels, trophozoites mimicked "pitting," a normal process in the body where spleen beds remove parasites without destroying the red cell. Schizont forms failed to traverse even 6-microm channels and rapidly formed a capillary blockage. Interestingly, individual uninfected red blood cells readily squeezed through the blockages formed by immobile schizonts in a 6-microm capillary. The last observation can explain the high parasitemia in a growing capillary blockage and the well known benefits of early blood transfusion in severe malaria.
Authors: J. Patrick Shelby, John White, Karthikeyan Ganesan, Pradipsinh K. Rathod, Daniel T. Chiu
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Ellison Medical Foundation, Bill and Melinda Gates Foundation, W. M. Keck Foundation, Camille and Henry Dreyfus Foundation, University of Washington, National Institutes of Health, American Chemical Society Petroleum Research Fund, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, Division of Graduate Education
OpenAlex ID: W2098708326