title: Experimental determination and computational interpretation of biophysical properties of lipid bilayers enriched by cholesteryl hemisuccinate.
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.
authors.affiliation: Department of Physics, Tampere University of Technology, P. O. Box 692, FI-33101 Tampere, Finland. Electronic address: waldemar.kulig@tut.fi.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Kulig
authors.affiliation: J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, v. v. i., Dolejskova 3, 18223 Prague 8, Czech Republic. Electronic address: piotr.jurkiewicz@jh-inst.cas.cz.
authors.forename: Piotr
authors.initials: P
authors.lastname: Jurkiewicz
authors.affiliation: J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, v. v. i., Dolejskova 3, 18223 Prague 8, Czech Republic.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Olżyńska
authors.affiliation: Department of Physics, Tampere University of Technology, P. O. Box 692, FI-33101 Tampere, Finland.
authors.forename: Joona
authors.initials: J
authors.lastname: Tynkkynen
authors.affiliation: Department of Physics, Tampere University of Technology, P. O. Box 692, FI-33101 Tampere, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Javanainen
authors.affiliation: Department of Physics, Tampere University of Technology, P. O. Box 692, FI-33101 Tampere, Finland.
authors.forename: Moutusi
authors.initials: M
authors.lastname: Manna
authors.affiliation: Department of Physics, Tampere University of Technology, P. O. Box 692, FI-33101 Tampere, Finland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Rog
authors.affiliation: J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, v. v. i., Dolejskova 3, 18223 Prague 8, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Hof
authors.affiliation: Department of Physics, Tampere University of Technology, P. O. Box 692, FI-33101 Tampere, Finland; MEMPHYS-Center for Biomembrane Physics, University of Southern Denmark, Odense, Denmark.
authors.forename: Ilpo
authors.initials: I
authors.lastname: Vattulainen
authors.affiliation: Department of Physics, Tampere University of Technology, P. O. Box 692, FI-33101 Tampere, Finland; Institute of Organic Chemistry Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 16610 Prague 6, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Jungwirth
mesh_terms: D015081:2-Naphthylamine / Q000031:analogs & derivatives / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry*; D002788:Cholesterol Esters / Q000737:chemistry*; D004095:Dihydropyridines / Q000737:chemistry; D007848:Laurates / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry; D011522:Protons; D014867:Water / Q000737:chemistry
chemical_list: C466879:2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid monomethyl ester; D002788:Cholesterol Esters; D004095:Dihydropyridines; D007848:Laurates; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D011522:Protons; D014867:Water; D002784:Cholesterol; D015081:2-Naphthylamine; C017251:1,2-oleoylphosphatidylcholine; C013440:cholesteryl succinate; C028694:1-palmitoyl-2-oleoylphosphatidylcholine; C065580:laurdan
keywords: Cholesterol-mimicking detergents; DPH; Dynamic light scattering; Laurdan; Molecular dynamics simulations; Time-dependent fluorescence shift