Single molecule and multiple bond characterization of catch bond associated cytoadhesion in malaria

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 wh...

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Autores principales:	Ying Bena Lim, Juzar Thingna, Jianshu Cao, Chwee Teck Lim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c7a788de5f4841c59bffc3720db6781f
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spelling	oai:doaj.org-article:c7a788de5f4841c59bffc3720db6781f2021-12-02T15:04:53ZSingle molecule and multiple bond characterization of catch bond associated cytoadhesion in malaria10.1038/s41598-017-04352-x2045-2322https://doaj.org/article/c7a788de5f4841c59bffc3720db6781f2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04352-xhttps://doaj.org/toc/2045-2322Abstract 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.Ying Bena LimJuzar ThingnaJianshu CaoChwee Teck LimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ying Bena Lim Juzar Thingna Jianshu Cao Chwee Teck Lim Single molecule and multiple bond characterization of catch bond associated cytoadhesion in malaria
description	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.
format	article
author	Ying Bena Lim Juzar Thingna Jianshu Cao Chwee Teck Lim
author_facet	Ying Bena Lim Juzar Thingna Jianshu Cao Chwee Teck Lim
author_sort	Ying Bena Lim
title	Single molecule and multiple bond characterization of catch bond associated cytoadhesion in malaria
title_short	Single molecule and multiple bond characterization of catch bond associated cytoadhesion in malaria
title_full	Single molecule and multiple bond characterization of catch bond associated cytoadhesion in malaria
title_fullStr	Single molecule and multiple bond characterization of catch bond associated cytoadhesion in malaria
title_full_unstemmed	Single molecule and multiple bond characterization of catch bond associated cytoadhesion in malaria
title_sort	single molecule and multiple bond characterization of catch bond associated cytoadhesion in malaria
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c7a788de5f4841c59bffc3720db6781f
work_keys_str_mv	AT yingbenalim singlemoleculeandmultiplebondcharacterizationofcatchbondassociatedcytoadhesioninmalaria AT juzarthingna singlemoleculeandmultiplebondcharacterizationofcatchbondassociatedcytoadhesioninmalaria AT jianshucao singlemoleculeandmultiplebondcharacterizationofcatchbondassociatedcytoadhesioninmalaria AT chweetecklim singlemoleculeandmultiplebondcharacterizationofcatchbondassociatedcytoadhesioninmalaria
_version_	1718389042045779968

Single molecule and multiple bond characterization of catch bond associated cytoadhesion in malaria

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