Influence of the membrane environment on cholesterol transfer

Breidigan, Jeffrey Michael; Krzyzanowski, Natalie; Liu, Yangmingyue; Porcar, Lionel; Perez-Salas, Ursula

doi:10.1194/jlr.m077909

Influence of the membrane environment on cholesterol transfer

Journal Article · Wed Oct 18 00:00:00 EDT 2017 · Journal of Lipid Research

DOI:https://doi.org/10.1194/jlr.m077909· OSTI ID:2469522

Breidigan, Jeffrey Michael ^[1]; Krzyzanowski, Natalie ^[1]; Liu, Yangmingyue ^[1]; Porcar, Lionel ^[2]; Perez-Salas, Ursula ^[1]

Univ. of Illinois, Chicago, IL (United States)
Inst. Laue-Langevin (ILL), Grenoble (France)

Cholesterol, an essential component in biological membranes, is highly unevenly distributed within the cell, with most localized in the plasma membrane while only a small fraction is found in the endoplasmic reticulum, where it is synthesized. Cellular membranes differ in lipid composition and protein content, and these differences can exist across their leaflets too. This thermodynamic landscape that cellular membranes impose on cholesterol is expected to modulate its transport. To uncover the role the membrane environment has on cholesterol inter- and intra-membrane movement, we used time-resolved small angle neutron scattering to study the passive movement of cholesterol between and within membranes with varying degrees of saturation content. We found that cholesterol moves systematically slower as the degree of saturation in the membranes increases, from a palmitoyl oleyl phosphotidylcholine membrane, which is unsaturated, to a dipalmitoylphosphatidylcholine (DPPC) membrane, which is fully saturated. Additionally, we found that the energetic barrier to move cholesterol in these phosphatidylcholine membranes is independent of their relative lipid composition and remains constant for both flip-flop and exchange at ~100 kJ/mol. Further, by replacing DPPC with the saturated lipid palmitoylsphingomyelin, an abundant saturated lipid of the outer leaflet of the plasma membrane, we found the rates decreased by a factor of two. This finding is in stark contrast with recent molecular dynamic simulations that predict a dramatic slow-down of seven orders of magnitude for cholesterol flipping in membranes with a similar phosphocholine and SM lipid composition.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Science Foundation (NSF); USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2469522

Journal Information:: Journal of Lipid Research, Journal Name: Journal of Lipid Research Journal Issue: 12 Vol. 58; ISSN 0022-2275

Publisher:: American Society for Biochemistry and Molecular BiologyCopyright Statement

Country of Publication:: United States

Language:: English

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