Nanofocused Scanning X-ray Fluorescence Microscopy Revealing an Effect of Heterozygous Hemoglobin S and C on Biochemical Activities in Plasmodium falciparum-Infected Erythrocytes
Abstract
While there is ample evidence suggesting that carriers of heterozygous hemoglobin S and C are protected from life-threatening malaria, little is known about the underlying biochemical mechanisms at the single cell level. In this work, using nanofocused scanning X-ray fluorescence microscopy, we quantify the spatial distribution of individual elements in subcellular compartments, including Fe, S, P, Zn, and Cu, in Plasmodium falciparum-infected (P. falciparum-infected) erythrocytes carrying the wild type or variant hemoglobins. Our data indicate that heterozygous hemoglobin S and C significantly modulate biochemical reactions in parasitized erythrocytes, such as aberrant hemozoin mineralization and a delay in hemoglobin degradation. The label-free scanning X-ray fluorescence imaging has great potential to quantify the spatial distribution of elements in subcellular compartments of P. falciparum-infected erythrocytes and unravel the biochemical mechanisms underpinning disease and protective traits.
- Authors:
-
- Heidelberg Univ. (Germany)
- European Synchrotron Radiation Facility (ESRF), Grenoble (France); Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II)
- Universitätsklinikum Heidelberg (Germany)
- The European Synchrotron Radiation Facility (ESRF), 38043 Grenoble, France
- Heidelberg Univ. (Germany); Kyoto Univ. (Japan)
- Publication Date:
- Research Org.:
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); German Research Foundation (DFG); Germany’s Excellence Strategy; Japan Society for the Promotion of Science (JSPS); Nakatani Foundation
- OSTI Identifier:
- 1646582
- Report Number(s):
- BNL-216237-2020-JAAM
Journal ID: ISSN 0003-2700
- Grant/Contract Number:
- SC0012704; SFB1129 P3; 2082/1-390761711
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Analytical Chemistry
- Additional Journal Information:
- Journal Volume: 92; Journal Issue: 8; Journal ID: ISSN 0003-2700
- Publisher:
- American Chemical Society (ACS)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Elements; Infectious diseases; Peptides and proteins; Fluorescence; Parasites
Citation Formats
Fröhlich, Benjamin, Yang, Yang, Thoma, Judith, Czajor, Julian, Lansche, Christine, Sanchez, Cecilia, Lanzer, Michael, Cloetens, Peter, and Tanaka, Motomu. Nanofocused Scanning X-ray Fluorescence Microscopy Revealing an Effect of Heterozygous Hemoglobin S and C on Biochemical Activities in Plasmodium falciparum-Infected Erythrocytes. United States: N. p., 2020.
Web. doi:10.1021/acs.analchem.9b05111.
Fröhlich, Benjamin, Yang, Yang, Thoma, Judith, Czajor, Julian, Lansche, Christine, Sanchez, Cecilia, Lanzer, Michael, Cloetens, Peter, & Tanaka, Motomu. Nanofocused Scanning X-ray Fluorescence Microscopy Revealing an Effect of Heterozygous Hemoglobin S and C on Biochemical Activities in Plasmodium falciparum-Infected Erythrocytes. United States. https://doi.org/10.1021/acs.analchem.9b05111
Fröhlich, Benjamin, Yang, Yang, Thoma, Judith, Czajor, Julian, Lansche, Christine, Sanchez, Cecilia, Lanzer, Michael, Cloetens, Peter, and Tanaka, Motomu. Mon .
"Nanofocused Scanning X-ray Fluorescence Microscopy Revealing an Effect of Heterozygous Hemoglobin S and C on Biochemical Activities in Plasmodium falciparum-Infected Erythrocytes". United States. https://doi.org/10.1021/acs.analchem.9b05111. https://www.osti.gov/servlets/purl/1646582.
@article{osti_1646582,
title = {Nanofocused Scanning X-ray Fluorescence Microscopy Revealing an Effect of Heterozygous Hemoglobin S and C on Biochemical Activities in Plasmodium falciparum-Infected Erythrocytes},
author = {Fröhlich, Benjamin and Yang, Yang and Thoma, Judith and Czajor, Julian and Lansche, Christine and Sanchez, Cecilia and Lanzer, Michael and Cloetens, Peter and Tanaka, Motomu},
abstractNote = {While there is ample evidence suggesting that carriers of heterozygous hemoglobin S and C are protected from life-threatening malaria, little is known about the underlying biochemical mechanisms at the single cell level. In this work, using nanofocused scanning X-ray fluorescence microscopy, we quantify the spatial distribution of individual elements in subcellular compartments, including Fe, S, P, Zn, and Cu, in Plasmodium falciparum-infected (P. falciparum-infected) erythrocytes carrying the wild type or variant hemoglobins. Our data indicate that heterozygous hemoglobin S and C significantly modulate biochemical reactions in parasitized erythrocytes, such as aberrant hemozoin mineralization and a delay in hemoglobin degradation. The label-free scanning X-ray fluorescence imaging has great potential to quantify the spatial distribution of elements in subcellular compartments of P. falciparum-infected erythrocytes and unravel the biochemical mechanisms underpinning disease and protective traits.},
doi = {10.1021/acs.analchem.9b05111},
journal = {Analytical Chemistry},
number = 8,
volume = 92,
place = {United States},
year = {Mon Mar 23 00:00:00 EDT 2020},
month = {Mon Mar 23 00:00:00 EDT 2020}
}
Web of Science
Works referenced in this record:
Is Hemoglobin an Essential Structural Component of Human Erythrocyte Membranes?*
journal, April 1963
- Weed, Robert I.; Reed, Claude F.; Berg, George
- Journal of Clinical Investigation, Vol. 42, Issue 4
Hemoglobin degradation in malaria‐infected erythrocytes determined from live cell magnetophoresis
journal, February 2006
- Moore, Lee R.; Fujioka, Hisashi; Williams, P. Stephen
- The FASEB Journal, Vol. 20, Issue 6
Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis
journal, November 2010
- Piel, Frédéric B.; Patil, Anand P.; Howes, Rosalind E.
- Nature Communications, Vol. 1, Issue 1
Iron Storage within Dopamine Neurovesicles Revealed by Chemical Nano-Imaging
journal, September 2007
- Ortega, Richard; Cloetens, Peter; Devès, Guillaume
- PLoS ONE, Vol. 2, Issue 9
Trace element mapping of a single cell using a hard x-ray nanobeam focused by a Kirkpatrick-Baez mirror system
journal, March 2009
- Matsuyama, S.; Shimura, M.; Mimura, H.
- X-Ray Spectrometry, Vol. 38, Issue 2
Hard X-ray nanoprobe at beamline P06 at PETRA III
journal, May 2010
- Schroer, Christian G.; Boye, Pit; Feldkamp, Jan M.
- Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, Vol. 616, Issue 2-3
Two dimensional hard x-ray nanofocusing with crossed multilayer Laue lenses
journal, January 2011
- Yan, Hanfei; Rose, Volker; Shu, Deming
- Optics Express, Vol. 19, Issue 16
Efficient concentration of high-energy x-rays for diffraction-limited imaging resolution
journal, January 2017
- Cesar da Silva, Julio; Pacureanu, Alexandra; Yang, Yang
- Optica, Vol. 4, Issue 5
Three-Dimensional Correlative Imaging of a Malaria-Infected Cell with a Hard X-ray Nanoprobe
journal, May 2019
- Yang, Y.; Fus, F.; Pacureanu, A.
- Analytical Chemistry
Synchrotron X-Ray Fluorescence Nanoprobe Reveals Target Sites for Organo-Osmium Complex in Human Ovarian Cancer Cells
journal, January 2017
- Sanchez-Cano, Carlos; Romero-Canelón, Isolda; Yang, Yang
- Chemistry - A European Journal, Vol. 23, Issue 11
Holotomography: Quantitative phase tomography with micrometer resolution using hard synchrotron radiation x rays
journal, November 1999
- Cloetens, P.; Ludwig, W.; Baruchel, J.
- Applied Physics Letters, Vol. 75, Issue 19
A multiplatform code for the analysis of energy-dispersive X-ray fluorescence spectra
journal, January 2007
- Solé, V. A.; Papillon, E.; Cotte, M.
- Spectrochimica Acta Part B: Atomic Spectroscopy, Vol. 62, Issue 1
Fate of haem iron in the malaria parasite Plasmodium falciparum
journal, July 2002
- Egan, Timothy J.; Combrinck, Jill M.; Egan, Joanne
- Biochemical Journal, Vol. 365, Issue 2
The Structure of Human Hemoglobin
journal, August 1962
- Konigsberg, William; Hill, Robert J.
- Journal of Biological Chemistry, Vol. 237, Issue 8
l -Cysteine influx and efflux: A possible role for red blood cells in regulation of redox status of the plasma
journal, January 2006
- Yildiz, Deniz; Uslu, Ceylan; Cakir, Yeliz
- Free Radical Research, Vol. 40, Issue 5
Erythocyte phosphate content in Huntington's disease
journal, July 1982
- Sarpel, G.; Barp, A. N.; Lubansky, H. J.
- Neuroscience Letters, Vol. 31, Issue 1
The effect of phosphate loading on erythrocyte 2,3-bisphosphoglycerate levels
journal, September 2002
- Bremner, Kyla; Bubb, William A.; Kemp, Graham J.
- Clinica Chimica Acta, Vol. 323, Issue 1-2
Fluxes in “Free” and Total Zinc Are Essential for Progression of Intraerythrocytic Stages of Plasmodium falciparum
journal, June 2012
- Marvin, Rebecca G.; Wolford, Janet L.; Kidd, Matthew J.
- Chemistry & Biology, Vol. 19, Issue 6
Copper pathways in Plasmodium falciparum infected erythrocytes indicate an efflux role for the copper P-ATPase
journal, July 2004
- Rasoloson, Dominique; Shi, Lirong; Chong, Curtis R.
- Biochemical Journal, Vol. 381, Issue 3
Intraerythrocytic Plasmodium falciparum utilizes only a fraction of the amino acids derived from the digestion of host cell cytosol for the biosynthesis of its proteins
journal, February 2002
- Krugliak, Miriam; Zhang, Jianmin; Ginsburg, Hagai
- Molecular and Biochemical Parasitology, Vol. 119, Issue 2
Excess hemoglobin digestion and the osmotic stability ofPlasmodium falciparum–infected red blood cells
journal, May 2003
- Lew, Virgilio L.; Tiffert, Teresa; Ginsburg, Hagai
- Blood, Vol. 101, Issue 10
Differential time-dependent volumetric and surface area changes and delayed induction of new permeation pathways in P. falciparum -infected hemoglobinopathic erythrocytes: Volumeric and surface area changes in P. falciparum -infected erythrocytes
journal, August 2016
- Waldecker, Mailin; Dasanna, Anil K.; Lansche, Christine
- Cellular Microbiology, Vol. 19, Issue 2
Beyond hemoglobin polymerization: the red blood cell membrane and sickle disease pathophysiology
journal, January 1991
- Hebbel, Rp
- Blood, Vol. 77, Issue 2
Hemoglobin S and C affect protein export in Plasmodium falciparum-infected erythrocytes
journal, February 2015
- Kilian, N.; Srismith, S.; Dittmer, M.
- Biology Open, Vol. 4, Issue 3
The sickle cell trait affects contact dynamics and endothelial cell activation in Plasmodium falciparum-infected erythrocytes
journal, November 2018
- Lansche, Christine; Dasanna, Anil K.; Quadt, Katharina
- Communications Biology, Vol. 1, Issue 1
Hemoglobinopathies: Slicing the Gordian Knot of Plasmodium falciparum Malaria Pathogenesis
journal, May 2013
- Taylor, Steve M.; Cerami, Carla; Fairhurst, Rick M.
- PLoS Pathogens, Vol. 9, Issue 5
Abnormal PfEMP1/knob display on Plasmodium falciparum-infected erythrocytes containing hemoglobin variants: fresh insights into malaria pathogenesis and protection
journal, August 2012
- Fairhurst, Rick M.; Bess, Cameron D.; Krause, Michael A.
- Microbes and Infection, Vol. 14, Issue 10
Haemoglobin C protects against clinical Plasmodium falciparum malaria
journal, November 2001
- Modiano, David; Luoni, Gaia; Sirima, Bienvenu Sodiomon
- Nature, Vol. 414, Issue 6861
Human malaria parasites in continuous culture
journal, August 1976
- Trager, W.; Jensen, J.
- Science, Vol. 193, Issue 4254
Trans Stimulation Provides Evidence for a Drug Efflux Carrier as the Mechanism of Chloroquine Resistance in Plasmodium falciparum †
journal, August 2003
- Sanchez, Cecilia P.; Stein, Wilfred; Lanzer, Michael
- Biochemistry, Vol. 42, Issue 31
Synchronization of Plasmodium falciparum Erythrocytic Stages in Culture
journal, June 1979
- Lambros, Chris; Vanderberg, Jerome P.
- The Journal of Parasitology, Vol. 65, Issue 3
Lensless Tomographic Imaging of Near Surface Structures of Frozen Hydrated Malaria-Infected Human Erythrocytes by Coherent X-Ray Diffraction Microscopy
journal, October 2017
- Frank, Viktoria; Chushkin, Yuriy; Fröhlich, Benjamin
- Scientific Reports, Vol. 7, Issue 1