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Experimental determination and computational interpretation of biophysical properties of lipid bilayers enriched by cholesteryl hemisuccinate

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Details

Original languageEnglish
Pages (from-to)422-432
Number of pages11
JournalBiochimica et Biophysica Acta: Biomembranes
Volume1848
Issue number2
Early online date25 Oct 2014
DOIs
Publication statusPublished - 2015
Publication typeA1 Journal article-refereed

Abstract

Cholesteryl hemisuccinate (CHS) is one of the cholesterol-mimicking detergents not observed in nature. It is, however, widely used in protein crystallography, in biochemical studies of proteins, and in pharmacology. Here, we performed an extensive experimental and theoretical study on the behavior of CHS in lipid membranes rich in unsaturated phospholipids. We found that the deprotonated form of CHS (that is the predominant form under physiological conditions) does not mimic cholesterol very well. The protonated form of CHS does better in this regard, but also its ability to mimic the physical effects of cholesterol on lipid membranes is limited. Overall, although ordering and condensing effects characteristic to cholesterol are present in systems containing any form of CHS, their strength is appreciably weaker compared to cholesterol. Based on the considerable amount of experimental and atomistic simulation data, we conclude that these differences originate from the fact that the ester group of CHS does not anchor it in an optimal position at the water-membrane interface. The implications of these findings for considerations of protein-cholesterol interactions are briefly discussed.

Keywords

  • Cholesterol-mimicking detergents, DPH, Dynamic light scattering, Laurdan, Molecular dynamics simulations, Time-dependent fluorescence shift

Publication forum classification

Field of science, Statistics Finland