Probing the Cytoadherence of Malaria Infected Red Blood Cells under Flow
Malaria is one of the most widespread and deadly human parasitic diseases caused by the Plasmodium (P.) species with the P.falciparum being the most deadly. The parasites are capable of invading red blood cells (RBCs) during infection. At the late stage of parasites’ development, the parasites expor...
Main Authors: | , , , , , , |
---|---|
Other Authors: | |
Format: | Article |
Language: | en_US |
Published: |
Public Library of Science
2013
|
Online Access: | http://hdl.handle.net/1721.1/79409 https://orcid.org/0000-0001-7616-7809 |
_version_ | 1826199135979569152 |
---|---|
author | Xu, Xiaofeng Efremov, Artem K. Li, Ang Lai, Lipeng Dao, Ming Cao, Jianshu Lim, Chwee-Teck |
author2 | MIT-SUTD Collaboration Office |
author_facet | MIT-SUTD Collaboration Office Xu, Xiaofeng Efremov, Artem K. Li, Ang Lai, Lipeng Dao, Ming Cao, Jianshu Lim, Chwee-Teck |
author_sort | Xu, Xiaofeng |
collection | MIT |
description | Malaria is one of the most widespread and deadly human parasitic diseases caused by the Plasmodium (P.) species with the P.falciparum being the most deadly. The parasites are capable of invading red blood cells (RBCs) during infection. At the late stage of parasites’ development, the parasites export proteins to the infected RBCs (iRBC) membrane and bind to receptors of surface proteins on the endothelial cells that line microvasculature walls. Resulting adhesion of iRBCs to microvasculature is one of the main sources of most complications during malaria infection. Therefore, it is important to develop a versatile and simple experimental method to quantitatively investigate iRBCs cytoadhesion and binding kinetics. Here, we developed an advanced flow based adhesion assay to demonstrate that iRBC’s adhesion to endothelial CD36 receptor protein coated channels is a bistable process possessing a hysteresis loop. This finding confirms a recently developed model of cell adhesion which we used to fit our experimental data. We measured the contact area of iRBC under shear flow at different stages of infection using Total Internal Reflection Fluorescence (TIRF), and also adhesion receptor and ligand binding kinetics using Atomic Force Microscopy (AFM). With these parameters, we reproduced in our model the experimentally observed changes in adhesion properties of iRBCs accompanying parasite maturation and investigated the main mechanisms responsible for these changes, which are the contact area during the shear flow as well as the rupture area size. |
first_indexed | 2024-09-23T11:14:57Z |
format | Article |
id | mit-1721.1/79409 |
institution | Massachusetts Institute of Technology |
language | en_US |
last_indexed | 2024-09-23T11:14:57Z |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | dspace |
spelling | mit-1721.1/794092022-10-01T02:20:23Z Probing the Cytoadherence of Malaria Infected Red Blood Cells under Flow Xu, Xiaofeng Efremov, Artem K. Li, Ang Lai, Lipeng Dao, Ming Cao, Jianshu Lim, Chwee-Teck MIT-SUTD Collaboration Office Massachusetts Institute of Technology. Department of Chemistry Massachusetts Institute of Technology. Department of Materials Science and Engineering Singapore-MIT Alliance in Research and Technology (SMART) Lim, Chwee Teck Dao, Ming Efremov, Artem K. Xu, Xiaofeng Lai, Lipeng Li, Ang Cao, Jianshu Malaria is one of the most widespread and deadly human parasitic diseases caused by the Plasmodium (P.) species with the P.falciparum being the most deadly. The parasites are capable of invading red blood cells (RBCs) during infection. At the late stage of parasites’ development, the parasites export proteins to the infected RBCs (iRBC) membrane and bind to receptors of surface proteins on the endothelial cells that line microvasculature walls. Resulting adhesion of iRBCs to microvasculature is one of the main sources of most complications during malaria infection. Therefore, it is important to develop a versatile and simple experimental method to quantitatively investigate iRBCs cytoadhesion and binding kinetics. Here, we developed an advanced flow based adhesion assay to demonstrate that iRBC’s adhesion to endothelial CD36 receptor protein coated channels is a bistable process possessing a hysteresis loop. This finding confirms a recently developed model of cell adhesion which we used to fit our experimental data. We measured the contact area of iRBC under shear flow at different stages of infection using Total Internal Reflection Fluorescence (TIRF), and also adhesion receptor and ligand binding kinetics using Atomic Force Microscopy (AFM). With these parameters, we reproduced in our model the experimentally observed changes in adhesion properties of iRBCs accompanying parasite maturation and investigated the main mechanisms responsible for these changes, which are the contact area during the shear flow as well as the rupture area size. Global Enterprise for Micro-Mechanics and Molecular Medicine United States. Dept. of Defense (DOD-ARO (W 911 NF-09-0480)) Singapore–MIT Alliance for Research and Technology ((SMART) Fellowship) National Science Foundation (U.S.) (NSF Grant No.1112825) 2013-07-02T18:22:40Z 2013-07-02T18:22:40Z 2013-05 2013-01 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/79409 Xu, Xiaofeng, Artem K. Efremov, Ang Li, Lipeng Lai, Ming Dao, Chwee Teck Lim, and Jianshu Cao. Probing the Cytoadherence of Malaria Infected Red Blood Cells Under Flow. Edited by Georges Snounou. PLoS ONE 8, no. 5 (May 28, 2013): e64763. https://orcid.org/0000-0001-7616-7809 en_US http://dx.doi.org/10.1371/journal.pone.0064763 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
spellingShingle | Xu, Xiaofeng Efremov, Artem K. Li, Ang Lai, Lipeng Dao, Ming Cao, Jianshu Lim, Chwee-Teck Probing the Cytoadherence of Malaria Infected Red Blood Cells under Flow |
title | Probing the Cytoadherence of Malaria Infected Red Blood Cells under Flow |
title_full | Probing the Cytoadherence of Malaria Infected Red Blood Cells under Flow |
title_fullStr | Probing the Cytoadherence of Malaria Infected Red Blood Cells under Flow |
title_full_unstemmed | Probing the Cytoadherence of Malaria Infected Red Blood Cells under Flow |
title_short | Probing the Cytoadherence of Malaria Infected Red Blood Cells under Flow |
title_sort | probing the cytoadherence of malaria infected red blood cells under flow |
url | http://hdl.handle.net/1721.1/79409 https://orcid.org/0000-0001-7616-7809 |
work_keys_str_mv | AT xuxiaofeng probingthecytoadherenceofmalariainfectedredbloodcellsunderflow AT efremovartemk probingthecytoadherenceofmalariainfectedredbloodcellsunderflow AT liang probingthecytoadherenceofmalariainfectedredbloodcellsunderflow AT lailipeng probingthecytoadherenceofmalariainfectedredbloodcellsunderflow AT daoming probingthecytoadherenceofmalariainfectedredbloodcellsunderflow AT caojianshu probingthecytoadherenceofmalariainfectedredbloodcellsunderflow AT limchweeteck probingthecytoadherenceofmalariainfectedredbloodcellsunderflow |