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The effects of N-acyl chain methylations on ceramide molecular properties in bilayer membranes

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Abstract

Long-chain saturated ceramides possess the ability to form gel domains in fluid bilayer membranes. Such domains may also contain sphingomyelin, but generally exclude cholesterol. We studied the effect of N-acyl chain methylations on the ability of ceramide to form ceramide- and sphingomyelin-containing gel domains that displace sterol. Fluorescence quenching of probes displaying different lateral partitioning in heterogeneous lipid bilayers showed that the methyl branches induced position-dependent changes in the lateral distribution of the ceramides. Distally monomethylated ceramides interacted with sphingomyelin and displaced sterol, whereas proximally monomethylated and polymethylated ceramides appeared to be located outside of sterol/sphingomyelin-enriched domains. The branched ceramides also markedly reduced the bilayer affinity for sterol as determined from the equilibrium partitioning of sterol between lipid vesicles and cyclodextrin. Altogether, alterations in intermolecular interactions induced by the methyl branches markedly affected the molecular properties of ceramide in artificial bilayers.

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Abbreviations

(P)SM:

(Palmitoyl-)sphingomyelin

PCer:

Palmitoyl-ceramide

10MeCer:

N-10-methyl-hexadecanoyl-ceramide

15MeCer:

N-15-methyl-heptadecanoyl-ceramide

16MeCer:

N-16-methyl-heptadecanoyl-ceramide

PhytCer:

N-3,7,11,15-methyl-hexadecanoyl-ceramide

tPA:

Trans-parinaric acid

CTL:

Cholestatrienol

CHL:

Cholesterol

References

  • Alanko SM, Halling KK, Maunula S, Slotte JP, Ramstedt B (2005) Displacement of sterols from sterol/sphingomyelin domains in fluid bilayer membranes by competing molecules. Biochim Biophys Acta 1715:111–121

    Article  PubMed  CAS  Google Scholar 

  • Ben YV, Menashe M, Biltonen RL, Johnson ML, Barenholz Y (1987) Interaction of trans-parinaric acid with phosphatidylcholine bilayers: comparison with the effect of other fluorophores. Biochim Biophys Acta 904:117–124

    Article  Google Scholar 

  • Bittman R (1993) Chemical preparation of glycerolipids: a review of recent syntheses in Phospholipids Handbook. In: Cevec G (ed) Marcel Dekker, Inc., pp 154–155

  • Bjorkqvist YJ, Nyholm TK, Slotte JP, Ramstedt B (2005) Domain formation and stability in complex lipid bilayers as reported by cholestatrienol. Biophys J 88:4054–4063

    Article  PubMed  Google Scholar 

  • Busto JV, Sot J, Requejo-Isidro J, Goni FM, Alonso A (2010) Cholesterol displaces palmitoylceramide from its tight packing with palmitoylsphingomyelin in the absence of a liquid-disordered phase. Biophys J 99:1119–1128

    Article  PubMed  CAS  Google Scholar 

  • Castro BM, Silva LC, Fedorov A, de Almeida RF, Prieto M (2009) Cholesterol-rich fluid membranes solubilize ceramide domains: implications for the structure and dynamics of mammalian intracellular and plasma membranes. J Biol Chem 284:22978–22987

    Article  PubMed  CAS  Google Scholar 

  • Cohen R, Barenholz Y, Gatt S, Dagan A (1984) Preparation and characterization of well defined D-erythro sphingomyelins. Chem Phys Lipids 35:371–384

    Article  PubMed  CAS  Google Scholar 

  • Fischer RT, Stephenson FA, Shafiee A, Schroeder F (1984) delta 5, 7, 9(11)-Cholestatrien-3 beta-ol: a fluorescent cholesterol analogue. Chem Phys Lipids 36:1–14

    Article  PubMed  CAS  Google Scholar 

  • Hannun YA, Luberto C (2000) Ceramide in the eukaryotic stress response. Trends Cell Biol 10:73–80

    Article  PubMed  CAS  Google Scholar 

  • Jaikishan S, Bjorkbom A, Slotte JP (2010) Sphingomyelin analogs with branched N-acyl chains: the position of branching dramatically affects acyl chain order and sterol interactions in bilayer membranes. Biochim Biophys Acta 1798:1987–1994

    Article  PubMed  CAS  Google Scholar 

  • Karlsson KA, Samuelsson BE (1974) The structure of ceramide aminoethylphosphonate from the sea anemone, Metridium senile. Biochim Biophys Acta 337:204–213

    PubMed  CAS  Google Scholar 

  • Lofgren H, Pascher I (1977) Molecular arrangements of sphingolipids. The monolayer behaviour of ceramides. Chem Phys Lipids 20:273–284

    Article  PubMed  CAS  Google Scholar 

  • Massey JB (2001) Interaction of ceramides with phosphatidylcholine, sphingomyelin and sphingomyelin/cholesterol bilayers. Biochim Biophys Acta 1510:167–184

    Article  PubMed  CAS  Google Scholar 

  • Maula T, Westerlund B, Slotte JP (2009) Differential ability of cholesterol-enriched and gel phase domains to resist benzyl alcohol-induced fluidization in multilamellar lipid vesicles. Biochim Biophys Acta 1788:2454–2461

    Article  PubMed  CAS  Google Scholar 

  • Megha, London E (2004) Ceramide selectively displaces cholesterol from ordered lipid domains (rafts): implications for lipid raft structure and function. J Biol Chem 279:9997–10004

    PubMed  CAS  Google Scholar 

  • Megha, Sawatzki P, Kolter T, Bittman R, London E (2007) Effect of ceramide N-acyl chain and polar headgroup structure on the properties of ordered lipid domains (lipid rafts). Biochim Biophys Acta 1768:2205–2212

    Article  PubMed  CAS  Google Scholar 

  • Nybond S, Bjorkqvist YJ, Ramstedt B, Slotte JP (2005) Acyl chain length affects ceramide action on sterol/sphingomyelin-rich domains. Biochim Biophys Acta 1718:61–66

    Article  PubMed  CAS  Google Scholar 

  • Nyholm TK, Grandell PM, Westerlund B, Slotte JP (2010) Sterol affinity for bilayer membranes is affected by their ceramide content and the ceramide chain length. Biochim Biophys Acta 1798:1008–1013

    Article  PubMed  CAS  Google Scholar 

  • Nystrom JH, Lonnfors M, Nyholm TK (2010) Transmembrane peptides influence the affinity of sterols for phospholipid bilayers. Biophys J 99:526–533

    Article  PubMed  Google Scholar 

  • Oku H, Mimura K, Tokitsu Y, Onaga K, Iwasaki H, Chinen I (2000) Biased distribution of the branched-chain fatty acids in ceramides of vernix caseosa. Lipids 35:373–381

    Article  PubMed  CAS  Google Scholar 

  • Perry DK, Hannun YA (1998) The role of ceramide in cell signaling. Biochim Biophys Acta 1436:233–243

    PubMed  CAS  Google Scholar 

  • Silva L, de Almeida RF, Fedorov A, Matos AP, Prieto M (2006) Ceramide-platform formation and -induced biophysical changes in a fluid phospholipid membrane. Mol Membr Biol 23:137–148

    Article  PubMed  CAS  Google Scholar 

  • Sklar LA, Hudson BS, Simoni RD (1977) Conjugated polyene fatty acids as fluorescent probes: synthetic phospholipid membrane studies. Biochemistry 16:819–828

    Article  PubMed  CAS  Google Scholar 

  • Sot J, Ibarguren M, Busto JV, Montes LR, Goni FM, Alonso A (2008) Cholesterol displacement by ceramide in sphingomyelin-containing liquid-ordered domains, and generation of gel regions in giant lipidic vesicles. FEBS Lett 582:3230–3236

    Article  PubMed  CAS  Google Scholar 

  • Stancevic B, Kolesnick R (2010) Ceramide-rich platforms in transmembrane signaling. FEBS Lett 584:1728–1740

    Article  PubMed  CAS  Google Scholar 

  • Tanaka II, Matsuoka S, Murata M, Tachibana K (1998) A new ceramide with a novel branched-chain fatty acid isolated from the epiphytic dinoflagellate coolia monotis. J Nat Prod 61:685–688

    Article  PubMed  CAS  Google Scholar 

  • Tian XR, Tang HF, Li YS, Lin HW, Ma N, Zhang W, Yao MN (2009) Ceramides and cerebrosides from the marine bryozoan Bugula neritina inhabiting South China Sea. J Asian Nat Prod Res 11:1005–1012

    Article  PubMed  CAS  Google Scholar 

  • Yano I, Imaizumi S, Tomiyasu I, Yabuuchi E (1983) Separation and analysis of free ceramides containing 2-hydroxy fatty acids in Sphingobacterium species. FEMS Microbiol Lett 20:449–453

    Article  CAS  Google Scholar 

  • Yasugi E, Kasama T, Seyama Y (1987) Branched long chain bases in cerebrosides of the guinea pig Harderian gland. J Biochem 102:1477–1482

    PubMed  CAS  Google Scholar 

  • Yasugi E, Kasama T, Seyama Y (1988) Identification of 10-methylsphinganine in cerebrosides of the guinea pig harderian gland. J Biochem 103:889–893

    PubMed  CAS  Google Scholar 

  • Yasugi E, Kasama T, Seyama Y (1991) Composition of long chain bases in ceramide of the guinea pig Harderian gland. J Biochem 110:202–206

    PubMed  CAS  Google Scholar 

  • Yu C, Alterman M, Dobrowsky RT (2005) Ceramide displaces cholesterol from lipid rafts and decreases the association of the cholesterol binding protein caveolin-1. J Lipid Res 46:1678–1691

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Thomas Nyholm for help with analyzing some of the data and Shishir Jaikishan for some assistance with the quenching experiments. Financial support from the Sigrid Juselius Foundation, Oskar Öflund Foundation, Medicinska Understödsföreningen Liv och Hälsa, National Doctoral Programme in Informational and Structural Biology, and Åbo Akademi University is gratefully acknowledged.

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  1. Bakarne Urzelai

    Present address: Department of Biochemistry and Molecular Biology, University of the Basque Country, 48080, Bilbao, Spain

Authors and Affiliations

  1. Biochemistry, Department of Biosciences, Åbo Akademi University, Tykistökatu 6 A, 20520, Turku, Finland

    Terhi Maula, Bakarne Urzelai & J. Peter Slotte

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  1. Terhi Maula
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  2. Bakarne Urzelai
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Correspondence to Terhi Maula.

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Maula, T., Urzelai, B. & Peter Slotte, J. The effects of N-acyl chain methylations on ceramide molecular properties in bilayer membranes. Eur Biophys J 40, 857–863 (2011). https://doi.org/10.1007/s00249-011-0702-7

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  • DOI: https://doi.org/10.1007/s00249-011-0702-7

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