title: Lipid bilayer thickness determines cholesterol's location in model membranes.
abstract: Cholesterol is an essential biomolecule of animal cell membranes, and an important precursor for the biosynthesis of certain hormones and vitamins. It is also thought to play a key role in cell signaling processes associated with functional plasma membrane microdomains (domains enriched in cholesterol), commonly referred to as rafts. In all of these diverse biological phenomena, the transverse location of cholesterol in the membrane is almost certainly an important structural feature. Using a combination of neutron scattering and solid-state2H NMR, we have determined the location and orientation of cholesterol in phosphatidylcholine (PC) model membranes having fatty acids of different lengths and degrees of unsaturation. The data establish that cholesterol reorients rapidly about the bilayer normal in all the membranes studied, but is tilted and forced to span the bilayer midplane in the very thin bilayers. The possibility that cholesterol lies flat in the middle of bilayers, including those made from PC lipids containing polyunsaturated fatty acids (PUFAs), is ruled out. These results support the notion that hydrophobic thickness is the primary determinant of cholesterol's location in membranes.
authors: Department of Physics, Brock University, St. Catharines, Ontario L2S 3A1, Canada and Institute of Molecular Biosciences, University of Graz, Graz, Austria.
authors: Drew
authors: D
authors: Marquardt
authors: The Bredesen Center for Interdisciplinary Research and Graduate Education, University of Tennessee, Knoxville, Tennessee 37996, USA and Joint Institute for Biological Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, USA and Biology and Soft Matter Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, USA. katsarasj@ornl.gov.
authors: Frederick A
authors: FA
authors: Heberle
authors: Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, USA.
authors: Denise V
authors: DV
authors: Greathouse
authors: Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, USA.
authors: Roger E
authors: RE
authors: Koeppe
authors: Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, USA and Department of Biochemistry and Cellular & Molecular Biology, University of Tennessee, Knoxville, TN 37996, USA.
authors: Robert F
authors: RF
authors: Standaert
authors: Department of Physics, Brock University, St. Catharines, Ontario L2S 3A1, Canada.
authors: Brad J
authors: BJ
authors: Van Oosten
authors: Department of Physics, Brock University, St. Catharines, Ontario L2S 3A1, Canada.
authors: Thad A
authors: TA
authors: Harroun
authors: Department of Physics, Indiana University - Purdue University Indianapolis, Indianapolis, Indiana 46202, USA. swassall@iupui.edu.
authors: Jacob J
authors: JJ
authors: Kinnun
authors: Department of Physics, Indiana University - Purdue University Indianapolis, Indianapolis, Indiana 46202, USA. swassall@iupui.edu.
authors: Justin A
authors: JA
authors: Williams
authors: Department of Physics, Indiana University - Purdue University Indianapolis, Indianapolis, Indiana 46202, USA. swassall@iupui.edu.
authors: Stephen R
authors: SR
authors: Wassall
authors: Department of Physics, Brock University, St. Catharines, Ontario L2S 3A1, Canada and The Bredesen Center for Interdisciplinary Research and Graduate Education, University of Tennessee, Knoxville, Tennessee 37996, USA and Biology and Soft Matter Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, USA. katsarasj@ornl.gov and Shull Wollan Center-a Joint Institute for Neutron Sciences, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, USA and Department of Physics and Astronomy, University of Tennessee, Knoxville, Tennessee 37996, USA.
authors: John
authors: J
authors: Katsaras
mesh_terms: D002462:Cell Membrane / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D021962:Membrane Microdomains / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry*; D012441:Saccharomyces cerevisiae
chemical_list: D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D002784:Cholesterol