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Cholesterol dynamics in membranes of raft composition: a molecular point of view from 2H and 31P solid-state NMR.

Abstract：

:Lipidic membrane systems that have been reported to be composed of sphingomyelin (SM)-cholesterol (Chol) microdomains or "rafts" by Dietrich et al. [palmitoyloleoyl-phosphatidylcholine(POPC)/SM/Chol, 1/1/1; Dietrich, C., Bagatolli, L. A., Volovyk, Z. N., Thompson, N. L., Levi, M., Jacobson, K., and Gratton, E. (2001) Biophys. J. 80, 1417-1428] and by Schroeder et al. [SCRL: Liver-PC/Liver-phosphatidylethanolamine/SM/Cerebrosides/Chol, 1/1/1/1/2; Schroeder, R., London, E., and Brown, D. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 12130-12134] were investigated under the form of fully hydrated liposomes by the noninvasive solid-state (31)P and (2)H NMR method. Liposomes of binary lipid composition POPC/Chol and SM/Chol were also studied as boundary/control systems. All systems are found to be in the liquid-ordered phase (Lo) at physiological temperatures. Use of deuterium-labeled cholesterol afforded finding both the position of the sterol motional axis and its molecular order parameter. The axis of anisotropic rotation of cholesterol is such that the molecule is, on average, quasiperpendicular to the membrane plane, in all of the four systems investigated. Cholesterol order parameters greater than 0.8 are observed, indicating that the sterol is in a very motionally restricted environment in the temperature range 0-60 degrees C. The binary mixtures present "boundary" situations with the lowest values for POPC/Chol and the highest for SM/Chol. The SCRL raft mixture has the same ordering as the SM/Chol, i.e., the highest order parameter values over the temperature range. It demonstrates that in the SCRL mixture cholesterol dynamics is as in the binary system SM/Chol, therefore, suggesting that it might be depleted from the rest of the membrane to form complexes as if it were alone with SM. On the other hand, the mixture POPC/SM/Chol exhibits an intermediate ordering situation between those of SM/Chol and POPC/Chol. This strongly suggests that cholesterol could be in fast exchange, at the NMR time scale (milli- to microseconds), between two or more membrane regions of different dynamics and questions the statement of "rigid domains" made of SM and cholesterol in the model "raft" system POPC/SM/Chol.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Aussenac F,Tavares M,Dufourc EJ

doi

10.1021/bi026717b

subject

Has Abstract

pub_date

2003-02-18 00:00:00

pages

1383-90

issue

6

eissn

0006-2960

issn

1520-4995

journal_volume

42

pub_type

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