Lipid bilayer thickness determines cholesterols location in model membranes

Drew Marquardt; Frederick A. Heberle; Denise V. Greathouse; Roger E. Koeppe; Robert F. Standaert; Brad J. Van Oosten; Thad A. Harroun; Jacob J. Kinnun; Justin A. Williams; Stephen R. Wassall; John Katsaras

doi:10.1039/c6sm01777k

Lipid bilayer thickness determines cholesterols location in model membranes

Drew Marquardt, Frederick A. Heberle, Denise V. Greathouse, Roger E. Koeppe, Robert F. Standaert, Brad J. Van Oosten, Thad A. Harroun, Jacob J. Kinnun, Justin A. Williams, Stephen R. Wassall, John Katsaras

Research output: Contribution to journal › Article › peer-review

58 Scopus citations

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.

Original language	English
Pages (from-to)	9417-9428
Number of pages	12
Journal	Soft Matter
Volume	12
Issue number	47
DOIs	https://doi.org/10.1039/c6sm01777k
State	Published - 2016

Funding

We thank Professor Howard Riezman (University of Geneva) for the generous gift of the cholesterol-producing yeast strain and protocol. We thank Norbert Kučerka for discussions. Neutron scattering experiments were performed at the Canadian Neutron Beam Centre (Chalk River, ON). Simulations were performed using facilities of the Shared Hierarchical Academic Research Computing Network (SHARCNET: www.sharcnet.ca) and Compute/Calcul Canada. We acknowledge support from the Vanier Canadian Graduate Scholarship from the Natural Science and Engineering Research Council (NSERC, to D. M.); National Science Foundation (MCB 1327611 to D. V. G. and R. E. K.); the University of Tennessee-Oak Ridge National Laboratory (ORNL); Joint Institute of Biological Sciences (to F. A. H.); the NSERC Discovery Grant (to T. A. H.); the Shull Wollan Center—a Joint Institute for Neutron Sciences (to J. K. and F. A. H.); and the Department of Energy (DOE) Scientific User Facilities Division, Office of Basic Energy Sciences, contract no. DEAC05-00OR2275 (to J. K. and F. A. H.)

Funders	Funder number
Compute/Calcul Canada
Joint Institute for Neutron Sciences
Joint Institute of Biological Sciences
Shull Wollan Center
University of Tennessee-Oak Ridge National Laboratory
Vanier Canadian Graduate Scholarship from the Natural Science and Engineering Research Council
National Science Foundation	MCB 1327611, 1327611
National Science Foundation
U.S. Department of Energy
Basic Energy Sciences	DEAC05-00OR2275
Basic Energy Sciences
Oak Ridge National Laboratory
Natural Sciences and Engineering Research Council of Canada
Université de Genève

Access to Document

10.1039/c6sm01777k

Cite this

@article{561b1bab881c4e0ea0d2d62a86f850c5,

title = "Lipid bilayer thickness determines cholesterols 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.",

author = "Drew Marquardt and Heberle, {Frederick A.} and Greathouse, {Denise V.} and Koeppe, {Roger E.} and Standaert, {Robert F.} and {Van Oosten}, {Brad J.} and Harroun, {Thad A.} and Kinnun, {Jacob J.} and Williams, {Justin A.} and Wassall, {Stephen R.} and John Katsaras",

note = "Publisher Copyright: {\textcopyright} The Royal Society of Chemistry.",

year = "2016",

doi = "10.1039/c6sm01777k",

language = "English",

volume = "12",

pages = "9417--9428",

journal = "Soft Matter",

issn = "1744-683X",

publisher = "Royal Society of Chemistry",

number = "47",

}

TY - JOUR

T1 - Lipid bilayer thickness determines cholesterols location in model membranes

AU - Marquardt, Drew

AU - Heberle, Frederick A.

AU - Greathouse, Denise V.

AU - Koeppe, Roger E.

AU - Standaert, Robert F.

AU - Van Oosten, Brad J.

AU - Harroun, Thad A.

AU - Kinnun, Jacob J.

AU - Williams, Justin A.

AU - Wassall, Stephen R.

AU - Katsaras, John

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84999737969&partnerID=8YFLogxK

U2 - 10.1039/c6sm01777k

DO - 10.1039/c6sm01777k

M3 - Article

C2 - 27801465

AN - SCOPUS:84999737969

SN - 1744-683X

VL - 12

SP - 9417

EP - 9428

JO - Soft Matter

JF - Soft Matter

IS - 47

ER -

Lipid bilayer thickness determines cholesterols location in model membranes

Abstract

Funding

Access to Document

Other files and links

Fingerprint

Cite this