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. 1985 Oct 1;101(4):1591–1598. doi: 10.1083/jcb.101.4.1591

Biochemical studies on cell fusion. II. Control of fusion response by lipid alteration

PMCID: PMC2113917  PMID: 4044646

Abstract

The preceding communication (Roos, D.S. and P.W. Choppin, 1985, J. Cell Biol. 101:1578-1590) described the lipid composition of a series of mouse fibroblast cell lines which vary in susceptibility to the fusogenic effects of polyethylene glycol (PEG). Two alterations in lipid content were found to be directly correlated with resistance to PEG-induced cell fusion: increases in fatty acyl chain saturation, and the elevation of neutral glycerides, including an unusual ether-linked compound. In this study, we have probed the association between lipid composition and cell fusion through the use of fatty acid supplements to the cellular growth medium, and show that the fusibility of cells can be controlled by altering their acyl chain composition. The parental Clone 1D cells contain moderately unsaturated fatty acids with a ratio of saturates to polyunsaturates (S/P) approximately 1 and fuse virtually to completion following a standard PEG treatment. By contrast, the lipids of a highly fusion-resistant mutant cell line, F40, are highly saturated (S/P approximately 4). When the S/P ratio of Clone 1D cells was increased to approximate that normally found in F40 cells by growth in the presence of high concentrations of saturated fatty acids, they became highly resistant to PEG. Reduction of the S/P ratio of F40 cells by growth in cis-polyunsaturated fatty acids rendered them susceptible to fusion. Cell lines F8, F16, etc., which are normally intermediate between Clone 1D and F40 in both lipid composition and fusion response, can be altered in either direction (towards either increased or decreased susceptibility to fusion) by the addition of appropriate fatty acids to the growth medium. Although trans-unsaturated fatty acids have phase-transition temperatures roughly similar to saturated compounds, and might therefore be expected to affect membrane fluidity in a similar manner, trans-unsaturated fatty acids exerted the same effect as cis-unsaturates on the control of PEG-induced cell fusion. This observation suggests that the control of cell fusion by alteration of fatty acid content is not due to changes in membrane fluidity, and thus that the fatty acids are involved in some other way in the modulation of cell fusion.

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Selected References

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  1. Ahkong Q. F., Fisher D., Tampion W., Lucy J. A. The fusion of erythrocytes by fatty acids, esters, retinol and alpha-tocopherol. Biochem J. 1973 Sep;136(1):147–155. doi: 10.1042/bj1360147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benveniste J., Henson P. M., Cochrane C. G. Leukocyte-dependent histamine release from rabbit platelets. The role of IgE, basophils, and a platelet-activating factor. J Exp Med. 1972 Dec 1;136(6):1356–1377. doi: 10.1084/jem.136.6.1356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Billah M. M., Lapetina E. G. Rapid decrease of phosphatidylinositol 4,5-bisphosphate in thrombin-stimulated platelets. J Biol Chem. 1982 Nov 10;257(21):12705–12708. [PubMed] [Google Scholar]
  4. Blow A. M., Botham G. M., Fisher D., Goodall A. H., Tilcock C. P., Lucy J. A. Water and calcium ions in cell fusion induced by poly(ethylene glycol). FEBS Lett. 1978 Oct 15;94(2):305–310. doi: 10.1016/0014-5793(78)80963-6. [DOI] [PubMed] [Google Scholar]
  5. Cabot M. C., Synder F. Manipulation of alkylglycerolipid levels in cultured cells. Fatty alcohol versus alkylglycerol supplements. Biochim Biophys Acta. 1980 Mar 21;617(3):410–418. doi: 10.1016/0005-2760(80)90007-7. [DOI] [PubMed] [Google Scholar]
  6. Castle J. D., Castle A. M., Ma A. K., Stukenbrok H. An enhanced incorporation of fatty acid into phosphatidyl choline that parallels histamine discharge in mast cells. J Membr Biol. 1984;79(3):215–230. doi: 10.1007/BF01871061. [DOI] [PubMed] [Google Scholar]
  7. Chaudhury M. K., Ohki S. Correlation between membrane expansion and temperature-induced membrane fusion. Biochim Biophys Acta. 1981 Apr 6;642(2):365–374. doi: 10.1016/0005-2736(81)90452-1. [DOI] [PubMed] [Google Scholar]
  8. Cockcroft S., Gomperts B. D. Evidence for a role of phosphatidylinositol turnover in stimulus-secretion coupling. Studies with rat peritoneal mast cells. Biochem J. 1979 Mar 15;178(3):681–687. doi: 10.1042/bj1780681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Davidson R. L., O'Malley K. A., Wheeler T. B. Polyethylene glycol-induced mammalian cell hybridization: effect of polyethylene glycol molecular weight and concentration. Somatic Cell Genet. 1976 May;2(3):271–280. doi: 10.1007/BF01538965. [DOI] [PubMed] [Google Scholar]
  10. Ferguson K. A., Glaser M., Bayer W. H., Vagelos P. R. Alteration of fatty acid composition of LM cells by lipid supplementation and temperature. Biochemistry. 1975 Jan 14;14(1):146–151. doi: 10.1021/bi00672a025. [DOI] [PubMed] [Google Scholar]
  11. Hokin L. E. Dynamic aspects of phospholipids during protein secretion. Int Rev Cytol. 1968;23:187–208. doi: 10.1016/s0074-7696(08)60272-7. [DOI] [PubMed] [Google Scholar]
  12. Holmes K. V., Doller E. W., Behnke J. N. Analysis of the functions of coronavirus glycoproteins by differential inhibition of synthesis with tunicamycin. Adv Exp Med Biol. 1981;142:133–142. doi: 10.1007/978-1-4757-0456-3_11. [DOI] [PubMed] [Google Scholar]
  13. Homma M. Trypsin action on the growth of Sendai virus in tissue culture cells. II. Restoration of the hemolytic activity if L cell-borne Sendai virus by trypsin. J Virol. 1972 May;9(5):829–835. doi: 10.1128/jvi.9.5.829-835.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Honda K., Maeda Y., Sasakawa S., Ohno H., Tsuchida E. Activities of cell fusion and lysis of the hybrid type of chemical fusogens. (I). Structure and function of the promotor of cell fusion. Biochem Biophys Res Commun. 1981 May 15;100(1):442–448. doi: 10.1016/s0006-291x(81)80116-7. [DOI] [PubMed] [Google Scholar]
  15. Honda K., Maeda Y., Sasakawa S., Ohno H., Tsuchida E. The components contained in polyethylene glycol of commercial grade (PEG-6,000) as cell fusogen. Biochem Biophys Res Commun. 1981 Jul 16;101(1):165–171. doi: 10.1016/s0006-291x(81)80025-3. [DOI] [PubMed] [Google Scholar]
  16. Ishizaka T., Hirata F., Ishizaka K., Axelrod J. Stimulation of phospholipid methylation, Ca2+ influx, and histamine release by bridging of IgE receptors on rat mast cells. Proc Natl Acad Sci U S A. 1980 Apr;77(4):1903–1906. doi: 10.1073/pnas.77.4.1903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Karnovsky M. J. Lipid domains in biological membranes: their structural and functional perturbation by free fatty acids and the regulation of receptor mobility. Co-presidential address. Am J Pathol. 1979 Nov;97(2):212–221. [PMC free article] [PubMed] [Google Scholar]
  18. Kennerly D. A., Sullivan T. J., Sylwester P., Parker C. W. Diacylglycerol metabolism in mast cells: a potential role in membrane fusion and arachidonic acid release. J Exp Med. 1979 Oct 1;150(4):1039–1044. doi: 10.1084/jem.150.4.1039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kosower N. S., Kosower E. M., Wegman P. Membrane mobility agents. II. Active promoters of cell fusion. Biochim Biophys Acta. 1975 Sep 2;401(3):530–534. doi: 10.1016/0005-2736(75)90250-3. [DOI] [PubMed] [Google Scholar]
  20. Lyman G. H., Preisler H. D., Papahadjopoulos D. Membrane action of DMSO and other chemical inducers of Friend leukaemic cell differentiation. Nature. 1976 Jul 29;262(5567):361–363. doi: 10.1038/262360a0. [DOI] [PubMed] [Google Scholar]
  21. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  22. Noble A. G., Lee G. T., Sprague R., Parish M. L., Spear P. G. Anti-gD monoclonal antibodies inhibit cell fusion induced by herpes simplex virus type 1. Virology. 1983 Aug;129(1):218–224. doi: 10.1016/0042-6822(83)90409-9. [DOI] [PubMed] [Google Scholar]
  23. Pontecorvo G., Riddle P. N., Hales A. Time and mode of fusion of human fibroblasts treated with polyethylene glycol (PEG). Nature. 1977 Jan 20;265(5591):257–258. doi: 10.1038/265257a0. [DOI] [PubMed] [Google Scholar]
  24. Rittenhouse-Simmons S. Production of diglyceride from phosphatidylinositol in activated human platelets. J Clin Invest. 1979 Apr;63(4):580–587. doi: 10.1172/JCI109339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Robinson J. M., Roos D. S., Davidson R. L., Karnovsky M. J. Membrane alterations and other morphological features associated with polyethylene glycol-induced cell fusion. J Cell Sci. 1979 Dec;40:63–75. doi: 10.1242/jcs.40.1.63. [DOI] [PubMed] [Google Scholar]
  26. Roos D. S., Davidson R. L. Isolation of mouse cell lines resistant to the fusion-inducing effect of polyethylene glycol. Somatic Cell Genet. 1980 May;6(3):381–390. doi: 10.1007/BF01542790. [DOI] [PubMed] [Google Scholar]
  27. Roos D. S., Robinson J. M., Davidson R. L. Cell fusion and intramembrane particle distribution in polyethylene glycol-resistant cells. J Cell Biol. 1983 Sep;97(3):909–917. doi: 10.1083/jcb.97.3.909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rothblat G. H., Arbogast L. Y., Ouellette L., Howard B. V. Preparation of delipidized serum protein for use in cell culture systems. In Vitro. 1976 Aug;12(8):554–557. doi: 10.1007/BF02797438. [DOI] [PubMed] [Google Scholar]
  29. Scheid A., Choppin P. W. Identification of biological activities of paramyxovirus glycoproteins. Activation of cell fusion, hemolysis, and infectivity of proteolytic cleavage of an inactive precursor protein of Sendai virus. Virology. 1974 Feb;57(2):475–490. doi: 10.1016/0042-6822(74)90187-1. [DOI] [PubMed] [Google Scholar]
  30. Scott C. C., Heckman C. A., Snyder F. Regulation of ether lipids and their precursors in relation to glycolysis in cultured neoplastic cells. Biochim Biophys Acta. 1979 Nov 21;575(2):215–224. doi: 10.1016/0005-2760(79)90023-7. [DOI] [PubMed] [Google Scholar]
  31. Smith C. L., Ahkong Q. F., Fisher D., Lucy J. A. Is purified poly(ethylene glycol) able to induce cell fusion? Biochim Biophys Acta. 1982 Oct 22;692(1):109–114. doi: 10.1016/0005-2736(82)90508-9. [DOI] [PubMed] [Google Scholar]
  32. Spector A. A., Kiser R. E., Denning G. M., Koh S. W., DeBault L. E. Modification of the fatty acid composition of cultured human fibroblasts. J Lipid Res. 1979 May;20(4):536–547. [PubMed] [Google Scholar]
  33. Stubbs C. D., Smith A. D. The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function. Biochim Biophys Acta. 1984 Jan 27;779(1):89–137. doi: 10.1016/0304-4157(84)90005-4. [DOI] [PubMed] [Google Scholar]
  34. Tilcock C. P., Fisher D. Interaction of phospholipid membranes with poly(ethylene glycol)s. Biochim Biophys Acta. 1979 Oct 19;557(1):53–61. doi: 10.1016/0005-2736(79)90089-0. [DOI] [PubMed] [Google Scholar]
  35. Wang E., Roos D. S., Heggeness M. H., Choppin P. W. Function of cytoplasmic fibers in syncytia. Cold Spring Harb Symp Quant Biol. 1982;46(Pt 2):997–1012. doi: 10.1101/sqb.1982.046.01.093. [DOI] [PubMed] [Google Scholar]
  36. Wright C. E., Shows T. B. Genetics of cell fusion: human chromosome 10 assignment of a gene (FUSE) that promotes polykaryocyte formation. Somatic Cell Genet. 1979 Jul;5(4):503–517. doi: 10.1007/BF01538884. [DOI] [PubMed] [Google Scholar]

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