Single molecule and multiple bond characterization of catch bond associated cytoadhesion in malaria
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Author(s)
Lim, Ying Bena
Thingna, Juzar
Cao, Jianshu
Lim, Chwee-Teck
Date Issued
June 2017
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Lim, Ying Bena et al. “Single Molecule and Multiple Bond Characterization of Catch Bond Associated Cytoadhesion in Malaria.” Scientific Reports 7, 1 (June 2017) © The Author(s) 2017
Abstract
The adhesion of malaria infected red blood cells (iRBCs) to host endothelial receptors in the microvasculature, or cytoadhesion, is associated with severe disease pathology such as multiple organ failure and cerebral malaria. Malaria iRBCs have been shown to bind to several receptors, of which intercellular adhesion molecule 1 (ICAM-1) upregulation in brain microvasculature is the only one correlated to cerebral malaria. We utilize a biophysical approach to study the interactions between iRBCs and ICAM-1. At the single molecule level, force spectroscopy experiments reveal that ICAM-1 forms catch bond interactions with Plasmodium falciparum parasite iRBCs. Flow experiments are subsequently conducted to understand multiple bond behavior. Using a robust model that smoothly transitions between our single and multiple bond results, we conclusively demonstrate that the catch bond behavior persists even under flow conditions. The parameters extracted from these experimental results revealed that the rate of association of iRBC-ICAM-1 bonds are ten times lower than iRBC-CD36 (cluster of differentiation 36), a receptor that shows no upregulation in the brains of cerebral malaria patients. Yet, the dissociation rates are nearly the same for both iRBC-receptor interactions. Thus, our results suggest that ICAM-1 may not be the sole mediator responsible for cytoadhesion in the brain.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Materials Science and Engineering
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Creative Commons Attribution 4.0 International
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DOI of Published Version
10.1038/s41598-017-04352-x
