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The lipid network

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Abstract

Natural cell membranes are composed of a remarkable variety of lipids, which provide specific biophysical properties to support membrane protein function. An improved understanding of this complexity of membrane composition may also allow the design of membrane active drugs. Crafting a relevant model of a cell membrane with controlled composition is becoming an art, with the ability to reveal the molecular mechanisms of biological processes and lead to better treatment of pathologies. By matching physiological observations from in vivo experiments to high-resolution information, more easily obtained from in vitro studies, complex interactions at the lipid interface are determined. The role of the lipid network in biological membranes is, therefore, the subject of increasing attention.

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References

  • Andersson DI, Hughes D (2011) Persistence of antibiotic resistance in bacterial populations. FEMS Microbiol Rev 35(5):901–911

    Article  PubMed  CAS  Google Scholar 

  • Andra J, Goldmann T, Ernst CM, Peschel A, Gutsmann T (2011) Multiple peptide resistance factor (MprF)-mediated Resistance of Staphylococcus aureus against antimicrobial peptides coincides with a modulated peptide interaction with artificial membranes comprising lysyl-phosphatidylglycerol. J Biol Chem 286(21):18692–18700

    Article  PubMed  Google Scholar 

  • Bagheri M, Keller S, Dathe M (2011) Interaction of W-substituted analogs of cyclo-RRRWFW with bacterial lipopolysaccharides: the role of the aromatic cluster in antimicrobial activity. Antimicrob Agents Chemother 55(2):788–797

    Article  PubMed  CAS  Google Scholar 

  • Bangham AD, Standish MM, Miller N (1965a) cation permeability of phospholipid model membranes - effect of narcotics. Nature 208(5017):1295

    Article  PubMed  CAS  Google Scholar 

  • Bangham AD, Standish MM, Watkins JC (1965b) Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 13(1):238–252

    Article  PubMed  CAS  Google Scholar 

  • Benson AA, Maruo B (1958) Piant phospholipids. I. Identification of the phosphatidyl glycerols. Biochim Biophys Acta 27(1):189–195

    Article  PubMed  CAS  Google Scholar 

  • Brown KL, Hancock RE (2006) Cationic host defense (antimicrobial) peptides. Curr Opin Immunol 18(1):24–30

    Article  PubMed  CAS  Google Scholar 

  • Canton R, Morosini MI (2011) Emergence and spread of antibiotic resistance following exposure to antibiotics. FEMS Microbiol Rev 35(5):977–991

    Article  PubMed  CAS  Google Scholar 

  • Cazzaniga E, Bulbarelli A, Lonati E, Orlando A, Re F, Gregori M, Masserini M (2011) Abeta peptide toxicity is reduced after treatments decreasing phosphatidylethanolamine content in differentiated neuroblastoma cells. Neurochem Res 36(5):863–869

    Article  PubMed  CAS  Google Scholar 

  • Cecchi C, Evangelisti E, Cascella R, Zampagni M, Benvenuti S, Luciani P, Deledda C, Cellai I, Wright D, Saccardi R, Peri A, Stefani M (2011) neuronal differentiation of human mesenchymal stromal cells increases their resistance to abeta42 aggregate toxicity. J Alzheimers Dis 27(3):651–664

    PubMed  CAS  Google Scholar 

  • Chapman D (1975) Phase transitions and fluidity characteristics of lipids and cell membranes. Q Rev Biophys 8(2):185–235

    Article  PubMed  CAS  Google Scholar 

  • Chapman D (1988) Biomembrane structure and function: recent studies and new techniques. Parasitology 96(Suppl):S11–S23

    Article  PubMed  Google Scholar 

  • Contreras FX, Ernst AM, Wieland F, Brugger B (2011) Specificity of intramembrane protein-lipid interactions. Cold Spring Harb Perspect Biol 3:a004705

    Article  PubMed  Google Scholar 

  • Cullis PR, de Kruijff B (1979) Lipid polymorphism and the functional roles of lipids in biological membranes. Biochim Biophys Acta 559(4):399–420

    Article  PubMed  CAS  Google Scholar 

  • Cullis PR, Verkleij AJ, Ververgaert PH (1978) Polymorphic phase behaviour of cardiolipin as detected by 31P NMR and freeze-fracture techniques. Effects of calcium, dibucaine and chlorpromazine. Biochim Biophys Acta 513(1):11–20

    Article  PubMed  CAS  Google Scholar 

  • Danielli JF, Davson H (1935) A contribution to the theory of permeability of thin films. J Cell Compar Physl 5(4):495–508

    Article  CAS  Google Scholar 

  • Di Paolo G, Kim TW (2011) Linking lipids to Alzheimer's disease: cholesterol and beyond. Nat Rev Neurosci 12(5):284–296

    Article  PubMed  Google Scholar 

  • Dufourc EJ, Smith IC, Jarrell HC (1983) A 2H-NMR analysis of dihydrosterculoyl-containing lipids in model membranes: structural effects of a cyclopropane ring. Chem Phys Lipids 33(2):153–177

    Article  PubMed  CAS  Google Scholar 

  • Epand RM (2007) Membrane lipid polymorphism: relationship to bilayer properties and protein function. Methods Mol Biol 400:15–26

    Article  PubMed  CAS  Google Scholar 

  • Epand RM, Epand RF (2011) Bacterial membrane lipids in the action of antimicrobial agents. J Pept Sci 17(5):298–305

    Article  PubMed  CAS  Google Scholar 

  • Fernandez DI, Sani MA, Gehman JD, Hahm KS, Separovic F (2011) Interactions of a synthetic Leu-Lys-rich antimicrobial peptide with phospholipid bilayers. Eur Biophys J 40(4):471–480

    Article  PubMed  CAS  Google Scholar 

  • Folch J (1942) Brain cephalin, a mixture of phosphatides. Separation from it of phosphatidyl serine, phosphatidyl ethanolamine, and a fraction containing an inositol phosphatide. J Biol Chem 146(1):35–44

    CAS  Google Scholar 

  • Fu R, Wang X, Li C, Santiago-Miranda AN, Pielak GJ, Tian F (2011) In situ structural characterization of a recombinant protein in native Escherichia coli membranes with solid-state magic-angle-spinning NMR. J Am Chem Soc 133(32):12370–12373

    Article  PubMed  CAS  Google Scholar 

  • Gehman JD, Separovic F (2011) Solid-state NMR of amyloid membrane interactions. Methods Mol Biol 752:165–177

    Article  PubMed  CAS  Google Scholar 

  • Gidalevitz D, Ishitsuka Y, Muresan AS, Konovalov O, Waring AJ, Lehrer RI, Lee KY (2003) Interaction of antimicrobial peptide protegrin with biomembranes. Proc Natl Acad Sci USA 100(11):6302–6307

    Article  PubMed  CAS  Google Scholar 

  • Gitler C, Rudy B (1972) Implications of membrane plasticity. Abstr Pap Am Chem S 164(Aug-S):214

    Google Scholar 

  • Gorter E, Grendel F (1925) On bimolecular layers of lipoids on the chromocytes of the blood. J Exp Med 41(4):439–443

    Article  PubMed  CAS  Google Scholar 

  • Greenberg ME, Li XM, Gugiu BG, Gu X, Qin J, Salomon RG, Hazen SL (2008) The lipid whisker model of the structure of oxidized cell membranes. J Biol Chem 283(4):2385–2396

    Article  PubMed  CAS  Google Scholar 

  • Grogan DW, Cronan JE Jr (1997) Cyclopropane ring formation in membrane lipids of bacteria. Microbiol Mol Biol Rev 61(4):429–441

    PubMed  CAS  Google Scholar 

  • Gustot A, Smriti, Ruysschaert JM, McHaourab H, Govaerts C (2010) Lipid composition regulates the orientation of transmembrane helices in HorA, an ABC multidrug transporter. J Biol Chem 285(19):14144–14151

    Article  PubMed  CAS  Google Scholar 

  • Hadley EB, Hancock RE (2010) Strategies for the discovery and advancement of novel cationic antimicrobial peptides. Curr Top Med Chem 10(18):1872–1881

    Article  PubMed  CAS  Google Scholar 

  • Hammer MU, Brauser A, Olak C, Brezesinski G, Goldmann T, Gutsmann T, Andra J (2010) Lipopolysaccharide interaction is decisive for the activity of the antimicrobial peptide NK-2 against Escherichia coli and Proteus mirabilis. Biochem J 427(3):477–488

    Article  PubMed  CAS  Google Scholar 

  • Huang C (1969) Studies on phosphatidylcholine vesicles. Formation and physical characteristics. Biochemistry 8(1):344–352

    Article  PubMed  CAS  Google Scholar 

  • Johnson RD, Schauerte JA, Wisser KC, Gafni A, Steel DG (2011) Direct observation of single amyloid-beta(1-40) oligomers on live cells: binding and growth at physiological concentrations. PLoS One 6(8):e23970

    Article  PubMed  CAS  Google Scholar 

  • Junkes C, Harvey RD, Bruce KD, Dolling R, Bagheri M, Dathe M (2011) Cyclic antimicrobial R-, W-rich peptides: the role of peptide structure and E. coli outer and inner membranes in activity and the mode of action. Eur Biophys J 40(4):515–528

    Article  PubMed  CAS  Google Scholar 

  • Karnovsky MJ, Kleinfeld AM, Hoover RL, Dawidowicz EA, McIntyre DE, Salzman EA, Klausner RD (1982) Lipid domains in membranes. Ann N Y Acad Sci 401:61–75

    Article  PubMed  CAS  Google Scholar 

  • Klenk E, Padberg G (1962) On the gangliosides of horse erythrocytes. Hoppe Seylers Z Physiol Chem 327:249–255

    Article  PubMed  CAS  Google Scholar 

  • Koprivnjak T, Peschel A (2011) Bacterial resistance mechanisms against host defense peptides. Cell Mol Life Sci 68(13):2243–2254

    Article  PubMed  CAS  Google Scholar 

  • Kuhn R, Egge H (1963) Uber Ergebnisse Der Permethylierung Der Ganglioside Gi Und Gii. Chem Ber-Recl 96(12):3338

    Article  CAS  Google Scholar 

  • Kuhn R, Wiegandt H (1963) Die Konstitution Der Ganglioside Gii, Giii Und Giv. Z Naturforsch Pt B B 18(7):541

    CAS  Google Scholar 

  • LaBach JP, White DC (1969) Identification of ceramide phosphorylethanolamine and ceramide phosphorylglycerol in the lipids of an anaerobic bacterium. J Lipid Res 10(5):528–534

    PubMed  CAS  Google Scholar 

  • Lohner K (2009) New strategies for novel antibiotics: peptides targeting bacterial cell membranes. Gen Physiol Biophys 28(2):105–116

    Article  PubMed  CAS  Google Scholar 

  • Lohner K, Prossnigg F (2009) Biological activity and structural aspects of PGLa interaction with membrane mimetic systems. Biochim Biophys Acta 1788(8):1656–1666

    Article  PubMed  CAS  Google Scholar 

  • Lundbaek JA, Collingwood SA, Ingolfsson HI, Kapoor R, Andersen OS (2010) Lipid bilayer regulation of membrane protein function: gramicidin channels as molecular force probes. J R Soc Interf 7(44):373–395

    Article  CAS  Google Scholar 

  • Macdonald PM, Seelig J (1987) Calcium binding to mixed cardiolipin-phosphatidylcholine bilayers as studied by deuterium nuclear magnetic resonance. Biochemistry 26(19):6292–6298

    Article  PubMed  CAS  Google Scholar 

  • Macfarlane MG (1962) Characterization of lipoamino-acids as o-amino-acid esters of phosphatidyl-glycerol. Nature 196(4850):136

    Article  CAS  Google Scholar 

  • Maldonado AY, Burz DS, Shekhtman A (2011) In-cell NMR spectroscopy. Prog Nucl Magn Reson Spectrosc 59(3):197–212

    Article  PubMed  CAS  Google Scholar 

  • Marsh D (1991) General features of phospholipid phase transitions. Chem Phys Lipids 57(2–3):109–120

    Article  PubMed  CAS  Google Scholar 

  • Marsh D (2008) Protein modulation of lipids, and vice-versa, in membranes. Biochim Biophys Acta 1778(7–8):1545–1575

    PubMed  CAS  Google Scholar 

  • Palmer KJ, Schmitt FO (1941) X-ray diffraction studies of lipide emulsions. J Cell Compar Physl 17(3):385–394

    Article  CAS  Google Scholar 

  • Palmer KJ, Schmitt FO, Chargaff E (1941) X-ray diffraction studies of certain lipide-protein complexes. J Cell Compar Physl 18(1):43–47

    Article  CAS  Google Scholar 

  • Pangborn MC (1941) A new serologically active phospholipid from beef heart. Proc Soc Exp Biol Med 48(2):484–486

    CAS  Google Scholar 

  • Papahadjopoulos D, Miller N (1967) Phospholipid model membranes. I. Structural characteristics of hydrated liquid crystals. Biochim Biophys Acta 135(4):624–638

    Article  PubMed  CAS  Google Scholar 

  • Perly B, Smith IC, Jarrell HC (1985) Effects of replacement of a double bond by a cyclopropane ring in phosphatidylethanolamines: a 2H NMR study of phase transitions and molecular organization. Biochemistry 24(4):1055–1063

    Article  PubMed  CAS  Google Scholar 

  • Peschel A (2002) How do bacteria resist human antimicrobial peptides? Trends Microbiol 10(4):179–186

    Article  PubMed  CAS  Google Scholar 

  • Pizer FL, Ballou CE (1959) Studies on myo-inositol phosphates of natural origin. J Am Chem Soc 81(4):915–921

    Article  CAS  Google Scholar 

  • Porter NA, Wolf RA, Weenen H (1980) Free-radical oxidation of poly-unsaturated lecithins. Lipids 15(3):163–167

    Article  CAS  Google Scholar 

  • Robertson JD (1957) Some aspects of the ultrastructure of double membranes. Prog Neurobiol 2:1–22, discussion 22-30

    PubMed  CAS  Google Scholar 

  • Rothman JE, Lenard J (1977) Membrane asymmetry. Science 195(4280):743–753

    Article  PubMed  CAS  Google Scholar 

  • Sani MA, Keech O, Gardestrom P, Dufourc EJ, Grobner G (2009) Magic-angle phosphorus NMR of functional mitochondria: in situ monitoring of lipid response under apoptotic-like stress. FASEB J 23(9):2872–2878

    Article  PubMed  CAS  Google Scholar 

  • Sani MA, Gehman JD, Separovic F (2011a) Lipid matrix plays a role in Abeta fibril kinetics and morphology. FEBS Lett 585(5):749–754

    Article  PubMed  CAS  Google Scholar 

  • Sani MA, Whitwell TC, Separovic F (2011b) Lipid composition regulates the conformation and insertion of the antimicrobial peptide maculatin 1.1. Biochim Biophys Acta (in press)

  • Schneider T, Kruse T, Wimmer R, Wiedemann I, Sass V, Pag U, Jansen A, Nielsen AK, Mygind PH, Raventos DS, Neve S, Ravn B, Bonvin AM, De Maria L, Andersen AS, Gammelgaard LK, Sahl HG, Kristensen HH (2010) Plectasin, a fungal defensin, targets the bacterial cell wall precursor Lipid II. Science 328(5982):1168–1172

    Article  PubMed  CAS  Google Scholar 

  • Selenko P, Wagner G (2007) Looking into live cells with in-cell NMR spectroscopy. J Struct Biol 158(2):244–253

    Article  PubMed  CAS  Google Scholar 

  • Serber Z, Dotsch V (2001) In-cell NMR spectroscopy. Biochemistry 40(48):14317–14323

    Article  PubMed  CAS  Google Scholar 

  • Serber Z, Ledwidge R, Miller SM, Dotsch V (2001) Evaluation of parameters critical to observing proteins inside living Escherichia coli by in-cell NMR spectroscopy. J Am Chem Soc 123(37):8895–8901

    Article  PubMed  CAS  Google Scholar 

  • Serber Z, Selenko P, Hansel R, Reckel S, Lohr F, Ferrell JE Jr, Wagner G, Dotsch V (2006) Investigating macromolecules inside cultured and injected cells by in-cell NMR spectroscopy. Nat Protoc 1(6):2701–2709

    Article  PubMed  CAS  Google Scholar 

  • Sevcsik E, Pabst G, Jilek A, Lohner K (2007) How lipids influence the mode of action of membrane-active peptides. Biochim Biophys Acta 1768(10):2586–2595

    Article  PubMed  CAS  Google Scholar 

  • Shai Y (2002) Mode of action of membrane active antimicrobial peptides. Biopolymers 66(4):236–248

    Article  PubMed  CAS  Google Scholar 

  • Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387(6633):569–572

    Article  PubMed  CAS  Google Scholar 

  • Singer SJ, Nicolson GL (1972) The fluid mosaic model of the structure of cell membranes. Science 175(4023):720–731

    Article  PubMed  CAS  Google Scholar 

  • Sperry WM (1926) Lipid excretion. III. Further studies of the quantitative relations the fecal lipids. J Biol Chem 68(2):0357–0383

    CAS  Google Scholar 

  • Stier A, Sackmann E (1973) Spin labels as enzyme substrates. Heterogeneous lipid distribution in liver microsomal membranes. Biochim Biophys Acta 311(3):400–408

    Article  PubMed  CAS  Google Scholar 

  • Takayama K, Qureshi N, Mascagni P, Nashed MA, Anderson L, Raetz CR (1983) Fatty acyl derivatives of glucosamine 1-phosphate in Escherichia coli and their relation to lipid A. Complete structure of A diacyl GlcN-1-P found in a phosphatidylglycerol-deficient mutant. J Biol Chem 258(12):7379–7385

    PubMed  CAS  Google Scholar 

  • Verdon J, Labanowski J, Sahr T, Ferreira T, Lacombe C, Buchrieser C, Berjeaud JM, Hechard Y (2011) Fatty acid composition modulates sensitivity of Legionella pneumophila to warnericin RK, an antimicrobial peptide. Biochim Biophys Acta 1808(4):1146–1153

    Article  PubMed  CAS  Google Scholar 

  • Vitali B, Turroni S, Serina S, Sosio M, Vannini L, Candela M, Guerzoni ME, Brigidi P (2008) Molecular and phenotypic traits of in-vitro-selected mutants of Bifidobacterium resistant to rifaximin. Int J Antimicrob Agents 31(6):555–560

    Article  PubMed  CAS  Google Scholar 

  • Wiedemann I, Breukink E, van Kraaij C, Kuipers OP, Bierbaum G, de Kruijff B, Sahl HG (2001) Specific binding of nisin to the peptidoglycan precursor lipid II combines pore formation and inhibition of cell wall biosynthesis for potent antibiotic activity. J Biol Chem 276(3):1772–1779

    PubMed  CAS  Google Scholar 

  • Willumeit R, Kumpugdee M, Funari SS, Lohner K, Navas BP, Brandenburg K, Linser S, Andra J (2005) Structural rearrangement of model membranes by the peptide antibiotic NK-2. Biochim Biophys Acta 1669(2):125–134

    Article  PubMed  CAS  Google Scholar 

  • Wilmes M, Cammue BP, Sahl HG, Thevissen K (2011) Antibiotic activities of host defense peptides: more to it than lipid bilayer perturbation. Nat Prod Rep 28(8):1350–1358

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The work was supported by Australian Research Council Discovery grant DP0984815 and by a seed and early career research grants (University of Melbourne). I am also particularly grateful to Prof. Cristobal Dos Remedios for insightful discussions.

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  1. School of Chemistry, Bio21 Institute, University of Melbourne, Melbourne, VIC, 3010, Australia

    Marc-Antoine Sani, Frances Separovic & John D. Gehman

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  1. Marc-Antoine Sani
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  2. Frances Separovic
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  3. John D. Gehman
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Correspondence to Marc-Antoine Sani.

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Sani, MA., Separovic, F. & Gehman, J.D. The lipid network. Biophys Rev 4, 283–290 (2012). https://doi.org/10.1007/s12551-012-0071-1

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