Lipid bilayer thickness determines cholesterol's location in model membranes

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

doi:10.1039/C6SM01777K

Lipid bilayer thickness determines cholesterol's location in model membranes

Journal Article · Tue Oct 11 00:00:00 EDT 2016 · Soft Matter

DOI:https://doi.org/10.1039/C6SM01777K· OSTI ID:1344271

Marquardt, Drew ^[1]; Heberle, Frederick A. ^[2]; Greathouse, Denise V. ^[3]; Koeppe, II, Roger E. ^[3]; Standaert, Robert F. ^[4]; Van Oosten, Brad J. ^[5]; Harroun, Thad A. ^[5]; Kinnun, Jacob J. ^[6]; Williams, Justin A. ^[6]; Wassall, Stephen R. ^[6]; Katsaras, John ^[7]

Brock Univ., St. Catharines (Canada); Univ. of Graz, Graz (Austria)
Univ. of Tennessee, Knoxville, TN (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Univ. of Arkansas, Fayetteville, AR (United States)
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)
Brock Univ., St. Catharines (Canada)
Indiana Univ. - Purdue Univ. Indianapolis, Indianapolis, IN (United States)
Brock Univ., St. Catharines (Canada); Univ. of Tennessee, Knoxville, TN (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Indiana Univ. - Purdue Univ. Indianapolis, Indianapolis, IN (United States)

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-state ²H 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. Finally, these results support the notion that hydrophobic thickness is the primary determinant of cholesterol's location in membranes.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1344271

Journal Information:: Soft Matter, Journal Name: Soft Matter Journal Issue: 47 Vol. 12; ISSN SMOABF; ISSN 1744-683X

Publisher:: Royal Society of ChemistryCopyright Statement

Country of Publication:: United States

Language:: English

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