Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1980 May 1;85(2):283–291. doi: 10.1083/jcb.85.2.283

Effects of cholesterol on lipid organization in human erythrocyte membrane

PMCID: PMC2110611  PMID: 7372709

Abstract

The molar ratio of cholesterol to phospholipid (C/P) in human erythrocyte membrane is modified by incubating the cells with liposomes of various C/P ratios. The observed increase in cell surface area may be accounted for by the addition of cholesterol molecules. Fusion between liposomes and cells or attachment of liposomes to cells is not a significant factor in the alteration of C/P ratio. Onset temperatures for lipid phase separation in modified membranes are measured by electron diffraction. The onset temperature increases with decreasing C/P ration from 2 degrees C at C/P = 0.95 to 20 degrees C at C/P = 0.5. Redistribution of intramembrane particles is observed in membranes freeze-quenched from temperatures below the onset temperature. The heterogeneous distribution of intramembrane particles below the onset temperature suggests phase separation of lipid, with concomitant segregation of intramembrane protein into domains, even in the presence of an intact spectrin network.

Full Text

The Full Text of this article is available as a PDF (853.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Borochov H., Abbott R. E., Schachter D., Shinitzky M. Modulation of erythrocyte membrane proteins by membrane cholesterol and lipid fluidity. Biochemistry. 1979 Jan 23;18(2):251–255. doi: 10.1021/bi00569a002. [DOI] [PubMed] [Google Scholar]
  2. Bruckdorfer K. R., Demel R. A., De Gier J., van Deenen L. L. The effect of partial replacements of membrane cholesterol by other steroids on the osmotic fragility and glycerol permeability of erythrocytes. Biochim Biophys Acta. 1969 Jul 15;183(2):334–345. doi: 10.1016/0005-2736(69)90089-3. [DOI] [PubMed] [Google Scholar]
  3. Cooper R. A., Arner E. C., Wiley J. S., Shattil S. J. Modification of red cell membrane structure by cholesterol-rich lipid dispersions. A model for the primary spur cell defect. J Clin Invest. 1975 Jan;55(1):115–126. doi: 10.1172/JCI107901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cooper R. A., Leslie M. H., Fischkoff S., Shinitzky M., Shattil S. J. Factors influencing the lipid composition and fluidity of red cell membranes in vitro: production of red cells possessing more than two cholesterols per phospholipid. Biochemistry. 1978 Jan 24;17(2):327–331. doi: 10.1021/bi00595a021. [DOI] [PubMed] [Google Scholar]
  5. DODGE J. T., MITCHELL C., HANAHAN D. J. The preparation and chemical characteristics of hemoglobin-free ghosts of human erythrocytes. Arch Biochem Biophys. 1963 Jan;100:119–130. doi: 10.1016/0003-9861(63)90042-0. [DOI] [PubMed] [Google Scholar]
  6. Dijck P. W., Zoelen E. J., Seldenrijk R., Deenen L. L., Gier J. Calorimetric behaviour of individual phospholipid classes from human and bovine erythrocyte membranes. Chem Phys Lipids. 1976 Oct;17(2-3):336–343. doi: 10.1016/0009-3084(76)90078-5. [DOI] [PubMed] [Google Scholar]
  7. Elgsaeter A., Shotton D. M., Branton D. Intramembrane particle aggregation in erythrocyte ghosts. II. The influence of spectrin aggregation. Biochim Biophys Acta. 1976 Feb 19;426(1):101–122. doi: 10.1016/0005-2736(76)90433-8. [DOI] [PubMed] [Google Scholar]
  8. Fowler V., Branton D. Lateral mobility of human erythrocyte integral membrane proteins. Nature. 1977 Jul 7;268(5615):23–26. doi: 10.1038/268023a0. [DOI] [PubMed] [Google Scholar]
  9. Gerritsen W. J., Verkleij A. J., Van Deenen L. L. The lateral distribution of intramembrane particles in the erythrocyte membrane and recombinant vesicles. Biochim Biophys Acta. 1979 Jul 19;555(1):26–41. doi: 10.1016/0005-2736(79)90069-5. [DOI] [PubMed] [Google Scholar]
  10. Gershfeld N. L. Equilibrium studies of lecithin-cholesterol interactions I. Stoichiometry of lecithin-cholesterol complexes in bulk systems. Biophys J. 1978 Jun;22(3):469–488. doi: 10.1016/S0006-3495(78)85500-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gottlieb M. H., Eanes E. D. On phase transitions in erythrocyte membranes and extracted membrane lipids. Biochim Biophys Acta. 1974 Dec 24;373(3):519–522. doi: 10.1016/0005-2736(74)90033-9. [DOI] [PubMed] [Google Scholar]
  12. Grunze M., Deuticke B. Changes of membrane permeability due to extensive cholesterol depletion in mammalian erythrocytes. Biochim Biophys Acta. 1974 Jul 12;356(1):125–130. doi: 10.1016/0005-2736(74)90300-9. [DOI] [PubMed] [Google Scholar]
  13. Hui S. W. Electron diffraction studies of membranes. Biochim Biophys Acta. 1977 Nov 14;472(3-4):345–371. doi: 10.1016/0304-4157(77)90002-8. [DOI] [PubMed] [Google Scholar]
  14. Hui S. W., Strozewski C. M. Electron diffraction studies of human erythrocyte membrane and its lipid extracts. Effects of hydration, temperature and hydrolysis. Biochim Biophys Acta. 1979 Aug 23;555(3):417–425. doi: 10.1016/0005-2736(79)90395-x. [DOI] [PubMed] [Google Scholar]
  15. Höchli M., Hackenbrock C. R. Thermotropic lateral translational motion of intramembrane particles in the inner mitochondrial membrane and its inhibition by artificial peripheral proteins. J Cell Biol. 1977 Feb;72(2):278–291. doi: 10.1083/jcb.72.2.278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Inbar M., Shinitzky M. Cholesterol as a bioregulator in the development and inhibition of leukemia. Proc Natl Acad Sci U S A. 1974 Oct;71(10):4229–4231. doi: 10.1073/pnas.71.10.4229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jackson W. M., Kostyla J., Nordin J. H., Brandts J. F. Calorimetric study of protein transitions in human erythrocyte ghosts. Biochemistry. 1973 Sep 11;12(19):3662–3667. doi: 10.1021/bi00743a014. [DOI] [PubMed] [Google Scholar]
  18. Kleemann W., McConnell H. M. Interactions of proteins and cholesterol with lipids in bilayer membranes. Biochim Biophys Acta. 1976 Jan 21;419(2):206–222. doi: 10.1016/0005-2736(76)90347-3. [DOI] [PubMed] [Google Scholar]
  19. Lange Y., D'Alessandro J. S. Characterization of mechanisms for transfer of cholesterol between human erythrocytes and plasma. Biochemistry. 1977 Oct 4;16(20):4339–4343. doi: 10.1021/bi00639a002. [DOI] [PubMed] [Google Scholar]
  20. Martin F. J., MacDonald R. C. Lipid vesicle-cell interactions. I. Hemagglutination and hemolysis. J Cell Biol. 1976 Sep;70(3):494–505. doi: 10.1083/jcb.70.3.494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. McMillan P. N., Luftig R. B. Preservation of erythrocyte ghost ultrastructure achieved by various fixatives. Proc Natl Acad Sci U S A. 1973 Nov;70(11):3060–3064. doi: 10.1073/pnas.70.11.3060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pagano R. E., Takeichi M. Adhesion of phospholipid vesicles to Chinese hamster fibroblasts. Role of cell surface proteins. J Cell Biol. 1977 Aug;74(2):531–546. doi: 10.1083/jcb.74.2.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Papahadjopoulos D., Mayhew E., Poste G., Smith S., Vail W. J. Incorporation of lipid vesicles by mammalian cells provides a potential method for modifying cell behaviour. Nature. 1974 Nov 8;252(5479):163–166. doi: 10.1038/252163a0. [DOI] [PubMed] [Google Scholar]
  24. Pearson R. P., Hui S. W., Stewart T. P. Correlative statistical analysis and computer modelling of intramembraneous particle distributions in human erythrocyte membranes. Biochim Biophys Acta. 1979 Nov 2;557(2):265–282. doi: 10.1016/0005-2736(79)90326-2. [DOI] [PubMed] [Google Scholar]
  25. ROSE H. G., OKLANDER M. IMPROVED PROCEDURE FOR THE EXTRACTION OF LIPIDS FROM HUMAN ERYTHROCYTES. J Lipid Res. 1965 Jul;6:428–431. [PubMed] [Google Scholar]
  26. Rousselet A., Guthmann C., Matricon J., Bienvenue A., Devaux P. F. Study of the transverse diffusion of spin labeled phospholipids in biological membranes. I. Human red bloods cells. Biochim Biophys Acta. 1976 Mar 19;426(3):357–371. doi: 10.1016/0005-2736(76)90382-5. [DOI] [PubMed] [Google Scholar]
  27. Shiga T., Maeda N., Suda T., Kon K., Sekiya M. The decreased membrane fluidity of in vivo aged, human erythrocytes. A spin label study. Biochim Biophys Acta. 1979 May 3;553(1):84–95. doi: 10.1016/0005-2736(79)90032-4. [DOI] [PubMed] [Google Scholar]
  28. Shinitzky M. An efficient method for modulation of cholesterol level in cell membranes. FEBS Lett. 1978 Jan 15;85(2):317–320. doi: 10.1016/0014-5793(78)80482-7. [DOI] [PubMed] [Google Scholar]
  29. Stewart T. P., Hui S. W., Portis A. R., Jr, Papahadjopoulos D. Complex phase mixing of phosphatidylcholine and phosphatidylserine in multilamellar membrane vesicles. Biochim Biophys Acta. 1979 Sep 4;556(1):1–16. doi: 10.1016/0005-2736(79)90415-2. [DOI] [PubMed] [Google Scholar]
  30. Tanaka K. I., Ohnishi S. Heterogeneity in the fluidity of intact erythrocyte membrane and its homogenization upon hemolysis. Biochim Biophys Acta. 1976 Mar 5;426(2):218–231. doi: 10.1016/0005-2736(76)90333-3. [DOI] [PubMed] [Google Scholar]
  31. Verkleij A. J., Nauta I. L., Werre J. M., Mandersloot J. G., Reinders B., Ververgaert P. H., de Gier J. The fusion of abnormal plasma lipoprotein (LP-X) and the erythrocyte membrane in patients with cholestasis studied by electronmicroscopy. Biochim Biophys Acta. 1976 Jun 17;436(2):366–376. doi: 10.1016/0005-2736(76)90200-5. [DOI] [PubMed] [Google Scholar]
  32. Verma S. P., Wallach D. F. Multiple thermotropic state transitions in erythrocyte membranes. A laser-Raman study of the CH-stretching and acoustical regions. Biochim Biophys Acta. 1976 Jun 17;436(2):307–318. doi: 10.1016/0005-2736(76)90196-6. [DOI] [PubMed] [Google Scholar]
  33. Wiley J. S., Cooper R. A. Inhibition of cation cotransport by cholesterol enrichment of human red cell membranes. Biochim Biophys Acta. 1975 Dec 16;413(3):425–431. doi: 10.1016/0005-2736(75)90125-x. [DOI] [PubMed] [Google Scholar]
  34. Wunderlich F., Wallach D. F., Speth V., Fischer H. Differential effects of temperature on the nuclear and plasma membranes of lymphoid cells. A study by freeze-etch electron microscopy. Biochim Biophys Acta. 1974 Nov 27;373(1):34–43. doi: 10.1016/0005-2736(74)90102-3. [DOI] [PubMed] [Google Scholar]
  35. ZLATKIS A., ZAK B., BOYLE A. J. A new method for the direct determination of serum cholesterol. J Lab Clin Med. 1953 Mar;41(3):486–492. [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES