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Biophotonic techniques for the study of malaria-infected red blood cells

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Abstract

Investigation of the homeostasis of red blood cells upon infection by Plasmodium falciparum poses complex experimental challenges. Changes in red cell shape, volume, protein, and ion balance are difficult to quantify. In this article, we review a wide range of optical techniques for quantitative measurements of critical homeostatic parameters in malaria-infected red blood cells. Fluorescence lifetime imaging and tomographic phase microscopy, quantitative deconvolution microscopy, and X-ray microanalysis, are used to measure haemoglobin concentration, cell volume, and ion contents. Atomic force microscopy is briefly reviewed in the context of these optical methodologies. We also describe how optical tweezers and optical stretchers can be usefully applied to empower basic malaria research to yield diagnostic information on cell compliance changes upon malaria infection. The combined application of these techniques sheds new light on the detailed mechanisms of malaria infection providing potential for new diagnostic or therapeutic approaches.

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References

  1. Aikawa M (1997) Studies on falciparum malaria with atomic-force and surface-potential microscopes. Ann Trop Med Parasitol 91(7):689–692

    Article  PubMed  CAS  Google Scholar 

  2. Aikawa M, Kamanura K, Shiraishi S, Matsumoto Y, Arwati H, Torii M, Ito Y, Takeuchi T, Tandler B (1996) Membrane knobs of unfixed Plasmodium falciparum infected erythrocytes: new findings as revealed by atomic force microscopy and surface potential spectroscopy. Exp Parasitol 84(3):339–343

    Article  PubMed  CAS  Google Scholar 

  3. Akaki M, Nagayasu E, Nakano Y, Aikawa M (2002) Surface charge of Plasmodium falciparum merozoites as revealed by atomic force microscopy with surface potential spectroscopy. Parasitol Res 88(1):16–20

    Article  PubMed  CAS  Google Scholar 

  4. Allen RJ, Kirk K (2004) Cell volume control in the Plasmodium-infected erythrocyte. Trends Parasitol 20(1):7–10; discussion 10-1

    Article  PubMed  Google Scholar 

  5. Block SM (1990) Optical tweezers: a new tool for biophysics. In: Grinstein S, Foskett JK (ed) Noninvasive techniques in cell biology. Wiley-Liss, New York, p 375

  6. Boutet de Monvel J, Le Calvez S, Ulfendahl M (2001) Image restoration for confocal microscopy: improving the limits of deconvolution, with application to the visualization of the mammalian hearing organ. Biophys J 80(5):2455–2470

    Article  PubMed  CAS  Google Scholar 

  7. Bronkhorst PJ, Streekstra GJ, Grimbergen J, Nijhof EJ, Sixma JJ, Brakenhoff GJ (1995) A new method to study shape recovery of red blood cells using multiple optical trapping. Biophys J 69(5):1666–1673

    Article  PubMed  CAS  Google Scholar 

  8. Choi W, Fang-Yen C, Badizadegan K, Oh S, Lue N, Dasari RR, Feld MS (2007) Tomographic phase microscopy. Nat Methods 4(9):717–719

    Article  PubMed  CAS  Google Scholar 

  9. De Cian A, Grellier P, Mouray E, Depoix D, Bertrand H, Monchaud D, Teulade-Fichou MP, Mergny JL, Alberti P (2008) Plasmodium telomeric sequences: structure, stability and quadruplex targeting by small compounds. ChemBioChem 9(16):2730–2739

    Article  PubMed  CAS  Google Scholar 

  10. Degliesposti G, Kasam V, Da Costa A, Kang HK, Kim N, Kim DW, Breton V, Kim D, Rastelli G (2009) Design and discovery of plasmepsin II inhibitors using an automated workflow on large-scale grids. ChemMedChem 4(7):1164–1173

    Article  PubMed  CAS  Google Scholar 

  11. Dobbe JG, Hardeman MR, Streekstra GJ, Strackee J, Ince C, Grimbergen CA (2002) Analyzing red blood cell-deformability distributions. Blood Cells Mol Dis 28(3):373–384

    Article  PubMed  CAS  Google Scholar 

  12. Elder AD, Domin A, Schierle GSK, Lindon C, Pines J, Esposito A, Kaminski CF (2009) A quantitative protocol for dynamic measurements of protein interactions by Forster resonance energy transfer-sensitized fluorescence emission. J R Soc Interface 6:S59–S81

    Article  CAS  Google Scholar 

  13. Elder AD, Kaminski CF, Frank JH (2009) phi2FLIM: a technique for alias-free frequency domain fluorescence lifetime imaging. Optics Express 17(25):23181–23203

    Article  PubMed  CAS  Google Scholar 

  14. Elliott JL, Saliba KJ, Kirk K (2001) Transport of lactate and pyruvate in the intraerythrocytic malaria parasite, Plasmodium falciparum. Biochem J 355(Pt 3):733–739

    PubMed  CAS  Google Scholar 

  15. Elliott DA, McIntosh MT, Hosgood HD III, Chen S, Zhang G, Baevova P, Joiner KA (2008) Four distinct pathways of hemoglobin uptake in the malaria parasite Plasmodium falciparum. Proc Natl Acad Sci USA 105(7):2463–2468

    Article  PubMed  Google Scholar 

  16. Esposito A, Choimet J-B, Skepper J, Mauritz JM, Lew VL, Kaminski C, Tiffert T (2010) Quantitative imaging of human red blood cells infected with Plasmodium falciparum. Biophys J (in press)

  17. Esposito A, Tiffert T, Mauritz JMA, Schlachter S, Bannister LH, Kaminski CF, Lew VL (2008) FRET imaging of hemoglobin concentration in Plasmodium falciparum-infected red cells. PLoS ONE 3(11):e3780

    Article  PubMed  CAS  Google Scholar 

  18. Fernandez-Segura E, Warley A (2008) Electron probe X-ray microanalysis for the study of cell physiology. Methods Cell Biol 88:19–43

    Article  PubMed  CAS  Google Scholar 

  19. Francis LW, Lewis PD, Wright CJ, Conlan RS (2010) Atomic force microscopy comes of age. Biol Cell 102(2):133–143

    CAS  Google Scholar 

  20. Garcia CR, Takeuschi M, Yoshioka K, Miyamoto H (1997) Imaging Plasmodium falciparum-infected ghost and parasite by atomic force microscopy. J Struct Biol 119(2):92–98

    Article  PubMed  CAS  Google Scholar 

  21. Glushakova S, Yin D, Li T, Zimmerberg J (2005) Membrane transformation during malaria parasite release from human red blood cells. Curr Biol 15(18):1645–1650

    Article  PubMed  CAS  Google Scholar 

  22. Glushakova S, Yin D, Gartner N, Zimmerberg J (2007) Quantification of malaria parasite release from infected erythrocytes: inhibition by protein-free media. Malar J 6:61

    Article  PubMed  Google Scholar 

  23. Guck J, Ananthakrishnan R, Moon TJ, Cunningham CC, Kas J (2000) Optical deformability of soft biological dielectrics. Phys Rev Lett 84(23):5451–5454

    Article  PubMed  CAS  Google Scholar 

  24. Guck J, Ananthakrishnan R, Mahmood H, Moon TJ, Cunningham CC, Kas J (2001) The optical stretcher: a novel laser tool to micromanipulate cells. Biophys J 81(2):767–784

    Article  PubMed  CAS  Google Scholar 

  25. Guck J, Schinkinger S, Lincoln B, Wottawah F, Ebert S, Romeyke M, Lenz D, Erickson HM, Ananthakrishnan R, Mitchell D, Kas J, Ulvick S, Bilby C (2005) Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. Biophys J 88(5):3689–3698

    Article  PubMed  CAS  Google Scholar 

  26. Henon S, Lenormand G, Richert A, Gallet F (1999) A new determination of the shear modulus of the human erythrocyte membrane using optical tweezers. Biophys J 76(2):1145–1151

    Article  PubMed  CAS  Google Scholar 

  27. Kaminski CF (2005) Fluorescence imaging of reactive processes. Zeitschrift Fur Physikalische Chemie—Int J Res Phys Chem Chem Phys 219(6):747–774

    CAS  Google Scholar 

  28. Kasas S, Thomson NH, Smith BL, Hansma PK, Miklossy J, Hansma HG (1997) Biological applications of the AFM: from single molecules to organs. Int J Imaging Syst Technol 8(2):151–161

    Article  Google Scholar 

  29. Kirk K (2001) Membrane transport in the malaria-infected erythrocyte. Physiol Rev 81(2):495–537

    PubMed  CAS  Google Scholar 

  30. Kreysing MK, Kiessling T, Fritsch A, Dietrich C, Guck JR, Kas JA (2008) The optical cell rotator. Opt Express 16(21):16984–16992

    Article  PubMed  CAS  Google Scholar 

  31. Krugliak M, Zhang J, Ginsburg H (2002) 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. Mol Biochem Parasitol 119(2):249–256

    Article  PubMed  CAS  Google Scholar 

  32. Kuhn Y, Rohrbach P, Lanzer M (2007) Quantitative pH measurements in Plasmodium falciparum-infected erythrocytes using pHluorin. Cell Microbiol 9(4):1004–1013

    Article  PubMed  CAS  Google Scholar 

  33. Lautenschlager F, Paschke S, Schinkinger S, Bruel A, Beil M, Guck J (2009) The regulatory role of cell mechanics for migration of differentiating myeloid cells. Proc Natl Acad Sci USA 106(37):15696–15701

    Article  PubMed  Google Scholar 

  34. Lee P, Ye Z, Van Dyke K, Kirk RG (1988) X-ray microanalysis of Plasmodium falciparum and infected red blood cells: effects of qinghaosu and chloroquine on potassium, sodium, and phosphorus composition. Am J Trop Med Hyg 39(2):157–165

    PubMed  CAS  Google Scholar 

  35. Lew VL, Tiffert T (2007) Is invasion efficiency in malaria controlled by pre-invasion events? Trends Parasitol 23(10):481–484

    Article  PubMed  CAS  Google Scholar 

  36. Lew VL, Tiffert T, Ginsburg H (2003) Excess hemoglobin digestion and the osmotic stability of Plasmodium falciparum-infected red blood cells. Blood 101(10):4189–4194

    Article  PubMed  CAS  Google Scholar 

  37. Lincoln B, Schinkinger S, Travis K, Wottawah F, Ebert S, Sauer F, Guck J (2007) Reconfigurable microfluidic integration of a dual-beam laser trap with biomedical applications. Biomed Microdevices 9(5):703–710

    Article  PubMed  Google Scholar 

  38. Lincoln B, Wottawah F, Schinkinger S, Ebert S, Guck J (2007) High-throughput rheological measurements with an optical stretcher. Methods Cell Biol 83:397–423

    Article  PubMed  CAS  Google Scholar 

  39. Marinkovic M, Diez-Silva M, Pantic I, Fredberg JJ, Suresh S, Butler JP (2009) Febrile temperature leads to significant stiffening of Plasmodium falciparum parasitized erythrocytes. Am J Physiol Cell Physiol 296(1):C59–C64

    Article  PubMed  CAS  Google Scholar 

  40. Mauritz J, Tiffert T, Seear R, Lautenschlager F, Esposito A, Lew V, Guck J, Kaminski CF (2010) Detection of Plasmodium falciparum-infected red blood cells by optical stretching. J Biomed Opt 15:030517

    Article  PubMed  Google Scholar 

  41. Mauritz JM, Esposito A, Ginsburg H, Kaminski CF, Tiffert T, Lew VL (2009) The homeostasis of Plasmodium falciparum-infected red blood cells. PLoS Comput Biol 5(4):e1000339

    Article  PubMed  CAS  Google Scholar 

  42. Mens PF, van Overmeir C, Bonnet M, Dujardin JC, d’Alessandro U (2008) Real-time PCR/MCA assay using fluorescence resonance energy transfer for the genotyping of resistance related DHPS-540 mutations in Plasmodium falciparum. Malar J 7:48

    Article  PubMed  CAS  Google Scholar 

  43. Nagao E, Kaneko O, Dvorak JA (2000) Plasmodium falciparum-infected erythrocytes: qualitative and quantitative analyses of parasite-induced knobs by atomic force microscopy. J Struct Biol 130(1):34–44

    Article  PubMed  CAS  Google Scholar 

  44. Nagao E, Nishijima H, Akita S, Nakayama Y, Dvorak JA (2000) The cell biological application of carbon nanotube probes for atomic force microscopy: comparative studies of malaria-infected erythrocytes. J Electron Microsc 49(3):453–458

    CAS  Google Scholar 

  45. Nash GB, O’Brien E, Gordon-Smith EC, Dormandy JA (1989) Abnormalities in the mechanical properties of red blood cells caused by Plasmodium falciparum. Blood 74(2):855–861

    PubMed  CAS  Google Scholar 

  46. Park YK, Diez-Silva M, Popescu G, Lykotrafitis G, Choi WS, Feld MS, Suresh S (2008) Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum. Proc Natl Acad Sci USA 105(37):13730–13735

    Article  PubMed  Google Scholar 

  47. Peter M, Ameer-Beg SM (2004) Imaging molecular interactions by multiphoton FLIM. Biol Cell 96(3):231–236

    Article  PubMed  CAS  Google Scholar 

  48. Remmerbach TW, Wottawah F, Dietrich J, Lincoln B, Wittekind C, Guck J (2009) Oral cancer diagnosis by mechanical phenotyping. Cancer Res 69(5):1728–1732

    Article  PubMed  CAS  Google Scholar 

  49. Rohrbach P, Friedrich O, Hentschel J, Plattner H, Fink RH, Lanzer M (2005) Quantitative calcium measurements in subcellular compartments of Plasmodium falciparum-infected erythrocytes. J Biol Chem 280(30):27960–27969

    Article  PubMed  CAS  Google Scholar 

  50. Safeukui I, Millet P, Boucher S, Melinard L, Fregeville F, Receveur MC, Pistone T, Fialon P, Vincendeau P, Fleury H, Malvy D (2008) Evaluation of FRET real-time PCR assay for rapid detection and differentiation of Plasmodium species in returning travellers and migrants. Malar J 7:70

    Article  PubMed  CAS  Google Scholar 

  51. Saliba KJ, Horner HA, Kirk K (1998) Transport and metabolism of the essential vitamin pantothenic acid in human erythrocytes infected with the malaria parasite Plasmodium falciparum. J Biol Chem 273(17):10190–10195

    Article  PubMed  CAS  Google Scholar 

  52. Sleep J, Wilson D, Simmons R, Gratzer W (1999) Elasticity of the red cell membrane and its relation to hemolytic disorders: an optical tweezers study. Biophys J 77(6):3085–3095

    Article  PubMed  CAS  Google Scholar 

  53. Staines HM, Ellory JC, Kirk K (2001) Perturbation of the pump-leak balance for Na(+) and K(+) in malaria-infected erythrocytes. Am J Physiol Cell Physiol 280(6):C1576–C1587

    PubMed  CAS  Google Scholar 

  54. Suresh S (2006) Mechanical response of human red blood cells in health and disease: some structure-property-function relationships. J Mater Res 21(8):1871–1877

    Article  CAS  Google Scholar 

  55. Suresh S, Spatz J, Mills JP, Micoulet A, Dao M, Lim CT, Beil M, Seufferlein T (2005) Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria. Acta Biomater 1(1):15–30

    Article  PubMed  CAS  Google Scholar 

  56. Tokumasu F, Dvorak J (2003) Development and application of quantum dots for immunocytochemistry of human erythrocytes. J Microsc 211(Pt 3):256–261

    PubMed  CAS  Google Scholar 

  57. Tokumasu F, Fairhurst RM, Ostera GR, Brittain NJ, Hwang J, Wellems TE, Dvorak JA (2005) Band 3 modifications in Plasmodium falciparum-infected AA and CC erythrocytes assayed by autocorrelation analysis using quantum dots. J Cell Sci 118(Pt 5):1091–1098

    Article  PubMed  CAS  Google Scholar 

  58. Warley A (1997) X-ray microanalysis for biologists. In: Glauert AM (ed) Practical methods in electron microscopy, vol 16. Portland Press, London and Miami

  59. Warley A, Skepper JN (2000) Long freeze-drying times are not necessary during the preparation of thin sections for X-ray microanalysis. J Microsc 198(Pt 2):116–123

    Article  PubMed  CAS  Google Scholar 

  60. Yoon YZ, Kotar J, Yoon G, Cicuta P (2008) The nonlinear mechanical response of the red blood cell. Phys Biol 5(3):36007

    Article  Google Scholar 

  61. Zanner MA, Galey WR, Scaletti JV, Brahm J, Vander Jagt DL (1990) Water and urea transport in human erythrocytes infected with the malaria parasite Plasmodium falciparum. Mol Biochem Parasitol 40(2):269–278

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by funds from the EPSRC (EP/E059384), BBSRC (BB/E008542/1) and by a grant from the Isaac Newton Trust to TT. YZ is supported by the Korea Foundation for International Cooperation of Science & Technology (KICOS) through a grant provided by the Korean Ministry of Education Science & Technology (MEST) in 2009 (No. 2009-00591). AE is supported by the Engineering and Physical Sciences Research Council UK (EP/F044011/1).

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Author notes

  1. Alessandro Esposito

    Present address: MRC Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge, CB20XZ, UK

Authors and Affiliations

  1. Department of Chemical Engineering and Biotechnology, University of Cambridge, Pembroke Street, Cambridge, CB2 3RA, UK

    Jakob M. A. Mauritz, Alessandro Esposito & Clemens F. Kaminski

  2. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK

    Jakob M. A. Mauritz, Alessandro Esposito, Teresa Tiffert, Jeremy N. Skepper & Virgilio L. Lew

  3. Centre For Ultrastructural Imaging, King’s College London, London, UK

    Alice Warley

  4. Sector of Biological and Soft Systems, Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, UK

    Young-Zoon Yoon, Pietro Cicuta & Jochen R. Guck

  5. Department of Physics, Sungkyunkwan University, Suwon, 440-746, Korea

    Young-Zoon Yoon

  6. Nanoscience Center, University of Cambridge, Cambridge, UK

    Pietro Cicuta

  7. School for Advanced Optical Technologies, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

    Clemens F. Kaminski

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  1. Jakob M. A. Mauritz
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Correspondence to Clemens F. Kaminski.

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Mauritz, J.M.A., Esposito, A., Tiffert, T. et al. Biophotonic techniques for the study of malaria-infected red blood cells. Med Biol Eng Comput 48, 1055–1063 (2010). https://doi.org/10.1007/s11517-010-0668-0

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  • DOI: https://doi.org/10.1007/s11517-010-0668-0

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