The Contribution of Differential Scanning Calorimetry for the Study of Peptide/Lipid Interactions

  • Marie-Lise Jobin
  • Isabel D. AlvesEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1964)


Membrane-active peptides include a variety of molecules such as antimicrobial (AMP), cell-penetrating (CPP), viral, and amyloid peptides that are implicated in several pathologies. They constitute important targets because they are either at the basis of novel therapies (drug delivery for CPPs or antimicrobial activity for AMPs) or they are the agents causing these pathologies (viral and amyloid peptides). They all share the common property of interacting with the cellular lipid membrane in their mode of action. Therefore, a better understanding of the peptide/lipid (P/L) interaction is essential to help decipher their mechanism of action. Among the different biophysical methods that can be used to fully characterize P/L interactions, differential scanning calorimetry (DSC) allows determining the peptide effect on the lipid phase transitions, a property that reflects the P/L interaction mode. A general protocol for classical DSC experiments for P/L studies will be provided.

Key words

Membrane-active peptides Peptide/lipid interaction Differential scanning calorimetry Lipid phase transition Thermodynamic behavior 


  1. 1.
    Cullis PR, Fenske DB, Hope MJ (1996) Physical properties and functional roles of lipids in membranes. In: Vance DE, Vance JE (eds) Biochemistry of lipids, lipoproteins and membranes. Elsevier, Amsterdam, pp 1–32Google Scholar
  2. 2.
    Israelachvili JN, Mitchell DJ, Ninham BW (1977) Theory of self-assembly of lipid bilayers and vesicles. Biochim Biophys Acta 470:185–201CrossRefGoogle Scholar
  3. 3.
    Lee AG (1977) Lipid phase transitions and phase diagrams. I. Lipid phase transitions. Biochim Biophys Acta 472:237–281CrossRefGoogle Scholar
  4. 4.
    Lee AG (1977) Lipid phase transitions and phase diagrams. II. Mictures involving lipids. Biochim Biophys Acta 472:285–344CrossRefGoogle Scholar
  5. 5.
    McElhaney RN (1982) The use of differential scanning calorimetry and differential thermal analysis in studies of model and biological membranes. Chem Phys Lipids 30:229–259CrossRefGoogle Scholar
  6. 6.
    McIntosh TJ (1996) Hydration properties of lamellar and non-lamellar phases of phosphatidylcholine and phosphatidylethanolamine. Chem Phys Lipids 81:117–131CrossRefGoogle Scholar
  7. 7.
    Epand RM, Bryszewska M (1988) Modulation of the bilayer to hexagonal phase transition and solvation of phosphatidylethanolamines in aqueous salt solutions. Biochemistry 27:8776–8779CrossRefGoogle Scholar
  8. 8.
    McElhaney RN (1986) Differential scanning calorimetric studies of lipid-protein interactions in model membrane systems. Biochim Biophys Acta 864:361–421CrossRefGoogle Scholar
  9. 9.
    Seelig J (2004) Thermodynamics of lipid-peptide interactions. Biochim Biophys Acta 1666:40–50CrossRefGoogle Scholar
  10. 10.
    Heerklotz H (2004) The microcalorimetry of lipid membranes. J Phys Condens Matter 16:441–467CrossRefGoogle Scholar
  11. 11.
    Jimenez-Monreal AM, Villalain J, Aranda FJ, Gomez-Fernandez JC (1998) The phase behavior of aqueous dispersions of unsaturated mixtures of diacylglycerols and phospholipids. Biochim Biophys Acta 1373:209–219CrossRefGoogle Scholar
  12. 12.
    Epand RM, Bach D, Epand RF, Borochov N, Wachtel E (2001) A new high-temperature transition of crystalline cholesterol in mixtures with phosphatidylserine. Biophys J 81:1511–1520CrossRefGoogle Scholar
  13. 13.
    Lewis RN, Zhang YP, McElhaney RN (2005) Calorimetric and spectroscopic studies of the phase behavior and organization of lipid bilayer model membranes composed of binary mixtures of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol. Biochim Biophys Acta 1668:203–214CrossRefGoogle Scholar
  14. 14.
    Garidel P, Blume A (2000) Miscibility of phosphatidylethanolamine-phosphatidylglycerol mixtures as a function of pH and acyl chain length. Eur Biophys J 28:629–638CrossRefGoogle Scholar
  15. 15.
    Raudino A (1995) Lateral inhomogeneous lipid membranes: theoretical aspects. Adv Colloid Interf Sci 57:229–285CrossRefGoogle Scholar
  16. 16.
    Almeida PF (2009) Thermodynamics of lipid interactions in complex bilayers. Biochim Biophys Acta 1788:72–85CrossRefGoogle Scholar
  17. 17.
    Riske KA, Barroso RP, Vequi-Suplicy CC, Germano R, Henriques VB et al (2009) Lipid bilayer pre-transition as the beginning of the melting process. Biochim Biophys Acta 1788:954–963CrossRefGoogle Scholar
  18. 18.
    Lichtenberg D, Freire E, Schmidt CF, Barenholz Y, Felgner PL et al (1981) Effect of surface curvature on stability, thermodynamic behavior, and osmotic activity of dipalmitoylphosphatidylcholine single lamellar vesicles. Biochemistry 20:3462–3467CrossRefGoogle Scholar
  19. 19.
    Mason JT, Huang C, Biltonen RL (1983) Effect of liposomal size on the calorimetric behavior of mixed-chain phosphatidylcholine bilayer dispersions. Biochemistry 22:2013–2018CrossRefGoogle Scholar
  20. 20.
    Rouser G, Fkeischer S, Yamamoto A (1970) Two dimensional then layer chromatographic separation of polar lipids and determination of phospholipids by phosphorus analysis of spots. Lipids 5:494–496CrossRefGoogle Scholar
  21. 21.
    Lohner K, Prenner EJ (1999) Differential scanning calorimetry and X-ray diffraction studies of the specificity of the interaction of antimicrobial peptides with membrane-mimetic systems. Biochim Biophys Acta 1462:141–156CrossRefGoogle Scholar
  22. 22.
    Leidy C, Wolkers WF, Jorgensen K, Mouritsen OG, Crowe JH (2001) Lateral organization and domain formation in a two-component lipid membrane system. Biophys J 80:1819–1828CrossRefGoogle Scholar
  23. 23.
    Shimshick EJ, Kleemann W, Hubbell WL, McConnell HM (1973) Lateral phase separations in membranes. J Supramol Struct 1:285–294CrossRefGoogle Scholar
  24. 24.
    Joanne P, Galanth C, Goasdoue N, Nicolas P, Sagan S et al (2009) Lipid reorganization induced by membrane-active peptides probed using differential scanning calorimetry. Biochim Biophys Acta 1788:1772–1781CrossRefGoogle Scholar
  25. 25.
    Epand RM (2007) Detecting the presence of membrane domains using DSC. Biophys Chem 126:197–200CrossRefGoogle Scholar
  26. 26.
    Epand RF, Wang G, Berno B, Epand RM (2009) Lipid segregation explains selective toxicity of a series of fragments derived from the human cathelicidin LL-37. Antimicrob Agents Chemother 53:3705–3714CrossRefGoogle Scholar
  27. 27.
    Polozov IV, Polozova AI, Molotkovsky JG, Epand RM (1997) Amphipathic peptide affects the lateral domain organization of lipid bilayers. Biochim Biophys Acta 1328:125–139CrossRefGoogle Scholar
  28. 28.
    Alves ID, Goasdoue N, Correia I, Aubry S, Galanth C et al (2008) Membrane interaction and perturbation mechanisms induced by two cationic cell penetrating peptides with distinct charge distribution. Biochim Biophys Acta 1780:948–959CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute for Pharmacology and Toxicology, Rudolf Virchow Center—Bio-Imaging CenterUniversity of WürzburgWürzburgGermany
  2. 2.Chimie et Biologie des Membranes et Nanoobjets, CBMN CNRS UMR 5248, Université Bordeaux 1PessacFrance

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