Functional Application Areas

Membrane and Lipid Stability

Membrane and lipid structures are stabilized by non-covalent intramolecular and intermolecular interactions. Membrane function depends on the correct orientation. There have been rapid advances in structural biology and relating structure to biochemical function and mechanism. However, knowledge of lipid structure alone does not ensure accurate prediction of stability, function and biological activity. The complete characterization of a lipid or membrane requires stability determination, and the forces which lead to stability and correct folding.

Differential Scanning Calorimetry (DSC) is a powerful analytical tool which directly measures the stability and unfolding of membrane or lipid.  In DSC, the sample is heated at a constant rate, and there is a detectable heat change associated with thermal denaturation. 

A single DSC experiment can determine:

  • Transition midpoint (Tm)
  • Enthalpy (ΔH) and heat capacity change (ΔCp) associated with transition
  • Presence of multiple lipids
  • Different phase structures

A lipid or membrane in aqueous solution is in equilibrium between the ordered phase and the liquid crystalline phase, the Tm is the transition temperature between these two phases.  Pure lipids usually have very sharp melting transitions.  The transitions are broadened by presence of impurities, or shape fluctuations of vesicles.

DSC data, either used alone or in conjunction with structural data, can provide information on:

  • Effects of chain length, saturation, head group structure, etc on Tm and ΔH
  • Characteristics of phase transition is association with lipid raft formation
  • Membranes and vesicle structure and formation, using different lipid ratios
  • Effects of curvature strain on lipid membranes and vesicles
  • Effects of proteins, DNA and small molecule drugs on lipid membranes

References

Calorimetric detection of curvature strain in phospholipid bilayers.
Epand, R.M., Epand, R.F.
Biophys. J. 66, 1450-1482. (1994)

Structure, composition, and peptide binding properties of detergent soluble bilayers and detergent-resistant rafts.
Gandhavadi, M., Allende, D., Vidal, A., Simon, S.A., McIntosh, T.J.  
Biophys. J. 82, 1469-1482 (2002)

Triton promotes domain formation in lipid raft mixtures.
Heerklotz, H.
Biophys. J. 83, 2693-2701 (2002)
.
The microcalorimetry of lipid membranes.
Heerklotz, H.
J. Phys.: Condens. Matter 16 R441-R467 (2004)
   
Phosphatidylserine-containing membranes alter the thermal stability of prothrombin’s catalytic domain: A differential scanning microcalorimetry study.
Lentz, B.R., Zhou, C.M., Wu, J.R.
Biochemistry 33, 5460-5468. (1994)

Effect of variations in the structure of a polyleucine-based a-helical transmembrane peptide on its interaction with phosphatidylcholine bilayers.
Liu, F., Lewis, R.N.A.H., Hodges, R.S., McElhaney, R.N.
Biochemistry 41, 9197-9207 (2002)

Characterization of the thermotropic behavior and lateral organization of lipid-peptide mixtures by combined experimental and theoretical approach: Effects of hydrophobic mismatch and role of flanking residues.
Morein, S., Killian, J.A., Sperotto, M.M.
Biophys. J. 82, 1405-1417 (2002)

Biophysical and structural properties of DNA diC14-amidine complexes: Influence of the DNA/lipid ratio.
Pector, V., Bachmann, J., Maas, D., Vandenbranden, M., Ruysschaert, J.M.
J. Biol. Chem. 275, 29533-29538 (2000)

High temperature stabilization of DNA in complexes with cationic lipids.
Tarahovsky, Y.S., Rakhmanova, V.A., Epand, R.M., Macdonald, R.C.
Biophys. J. 82, 264-273 (2002)

Reference Lists

DSC – Lipid and Membrane Studies Reference List

DSC – Lipid-Protein Interactions Reference List

DSC – Lipid-Small Molecule Interactions Reference List

DSC – Nucleic Acid-Lipid Interactions Reference List

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