Abstract
A recent thermodynamic model describes a reversible reaction between cholesterol (C) and phospholipid (P) to form a condensed complex C(nq)P(np). Here q and p are relatively prime integers used to define the stoichiometric composition, and n is a measure of cooperativity. The present study applies this model to the scanning calorimetry of binary mixtures of cholesterol and saturated phosphatidylcholines, especially work by McElhaney and collaborators. These mixtures generally show two heat capacity peaks, a sharp peak and a broad peak. The sharp heat absorption is largely due to the chain melting transition of pure phospholipid. In the present work the broad heat absorption is attributed to the thermal dissociation of complexes. The best fits of the model to the data require the complex formation to be highly cooperative, with cooperativity n = 12. Detailed comparisons are made between model calculations and calorimetric data. A number of unusual features of the data arise naturally in the model. The principal discrepancy between the calculations and experimental results is a spurious calculated heat absorption peak. This discrepancy is related to the reported relative magnitudes of the integrated broad and sharp heat absorption curves.
Full Text
The Full Text of this article is available as a PDF (515.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Dietrich C., Bagatolli L. A., Volovyk Z. N., Thompson N. L., Levi M., Jacobson K., Gratton E. Lipid rafts reconstituted in model membranes. Biophys J. 2001 Mar;80(3):1417–1428. doi: 10.1016/S0006-3495(01)76114-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Engelman D. M., Rothman J. E. The planar organization of lecithin-cholesterol bilayers. J Biol Chem. 1972 Jun 10;247(11):3694–3697. [PubMed] [Google Scholar]
- FINEAN J. B. Phospholipid-cholesterol complex in the structure of myelin. Experientia. 1953 Jan 15;9(1):17–19. doi: 10.1007/BF02147697. [DOI] [PubMed] [Google Scholar]
- Hinz H. J., Sturtevant J. M. Calorimetric investigation of the influence of cholesterol on the transition properties of bilayers formed from synthetic L- -lecithins in aqueous suspension. J Biol Chem. 1972 Jun 10;247(11):3697–3700. [PubMed] [Google Scholar]
- Ipsen J. H., Karlström G., Mouritsen O. G., Wennerström H., Zuckermann M. J. Phase equilibria in the phosphatidylcholine-cholesterol system. Biochim Biophys Acta. 1987 Nov 27;905(1):162–172. doi: 10.1016/0005-2736(87)90020-4. [DOI] [PubMed] [Google Scholar]
- Ipsen J. H., Mouritsen O. G., Zuckermann M. J. Theory of thermal anomalies in the specific heat of lipid bilayers containing cholesterol. Biophys J. 1989 Oct;56(4):661–667. doi: 10.1016/S0006-3495(89)82713-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mabrey S., Mateo P. L., Sturtevant J. M. High-sensitivity scanning calorimetric study of mixtures of cholesterol with dimyristoyl- and dipalmitoylphosphatidylcholines. Biochemistry. 1978 Jun 13;17(12):2464–2468. doi: 10.1021/bi00605a034. [DOI] [PubMed] [Google Scholar]
- McMullen T. P., Lewis R. N., McElhaney R. N. Differential scanning calorimetric study of the effect of cholesterol on the thermotropic phase behavior of a homologous series of linear saturated phosphatidylcholines. Biochemistry. 1993 Jan 19;32(2):516–522. doi: 10.1021/bi00053a016. [DOI] [PubMed] [Google Scholar]
- Nielsen M., Miao L., Ipsen J. H., Zuckermann M. J., Mouritsen O. G. Off-lattice model for the phase behavior of lipid-cholesterol bilayers. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 1999 May;59(5 Pt B):5790–5803. doi: 10.1103/physreve.59.5790. [DOI] [PubMed] [Google Scholar]
- Presti F. T., Pace R. J., Chan S. I. Cholesterol-phospholipid interaction in membranes. 2. Stoichiometry and molecular packing of cholesterol-rich domains. Biochemistry. 1982 Aug 3;21(16):3831–3835. doi: 10.1021/bi00259a017. [DOI] [PubMed] [Google Scholar]
- Radhakrishnan A., McConnell H. M. Chemical activity of cholesterol in membranes. Biochemistry. 2000 Jul 18;39(28):8119–8124. doi: 10.1021/bi0005097. [DOI] [PubMed] [Google Scholar]
- Radhakrishnan A., McConnell H. M. Condensed complexes of cholesterol and phospholipids. Biophys J. 1999 Sep;77(3):1507–1517. doi: 10.1016/S0006-3495(99)76998-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Radhakrishnan A., McConnell H. M. Electric field effect on cholesterol-phospholipid complexes. Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1073–1078. doi: 10.1073/pnas.97.3.1073. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Recktenwald D. J., McConnell H. M. Phase equilibria in binary mixtures of phosphatidylcholine and cholesterol. Biochemistry. 1981 Jul 21;20(15):4505–4510. doi: 10.1021/bi00518a042. [DOI] [PubMed] [Google Scholar]
- Seelig A. Local anesthetics and pressure: a comparison of dibucaine binding to lipid monolayers and bilayers. Biochim Biophys Acta. 1987 May 29;899(2):196–204. doi: 10.1016/0005-2736(87)90400-7. [DOI] [PubMed] [Google Scholar]
- Somerharju P., Virtanen J. A., Cheng K. H. Lateral organisation of membrane lipids. The superlattice view. Biochim Biophys Acta. 1999 Aug 25;1440(1):32–48. doi: 10.1016/s1388-1981(99)00106-7. [DOI] [PubMed] [Google Scholar]
- Thewalt J. L., Bloom M. Phosphatidylcholine: cholesterol phase diagrams. Biophys J. 1992 Oct;63(4):1176–1181. doi: 10.1016/S0006-3495(92)81681-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vist M. R., Davis J. H. Phase equilibria of cholesterol/dipalmitoylphosphatidylcholine mixtures: 2H nuclear magnetic resonance and differential scanning calorimetry. Biochemistry. 1990 Jan 16;29(2):451–464. doi: 10.1021/bi00454a021. [DOI] [PubMed] [Google Scholar]
- Wang M. M., Sugar I. P., Chong P. L. Role of the sterol superlattice in the partitioning of the antifungal drug nystatin into lipid membranes. Biochemistry. 1998 Aug 25;37(34):11797–11805. doi: 10.1021/bi980290k. [DOI] [PubMed] [Google Scholar]