Influence of the membrane environment on cholesterol transfer
Autor: | Ursula Perez-Salas, Jeffrey Michael Breidigan, Natalie Krzyzanowski, Yangmingyue Liu, Lionel Porcar |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
1 2-Dipalmitoylphosphatidylcholine time resolved SANS QD415-436 lipid flip-flop 010402 general chemistry 01 natural sciences Biochemistry spontaneous lipid transport 03 medical and health sciences chemistry.chemical_compound Endocrinology Phosphatidylcholine Unilamellar Liposomes Research Articles Phosphocholine lipid exchange Cholesterol Endoplasmic reticulum Biological Transport Biological membrane Cell Biology Small-angle neutron scattering Sphingomyelins lipid vesicles 0104 chemical sciences Kinetics 030104 developmental biology Membrane chemistry cholesterol exchange Dipalmitoylphosphatidylcholine Phosphatidylcholines Biophysics Thermodynamics lipids (amino acids peptides and proteins) cholesterol flip-flop |
Zdroj: | 'Journal of Lipid Research ', vol: 58, pages: 2255-2263 (2017) Journal of Lipid Research Journal of Lipid Research, Vol 58, Iss 12, Pp 2255-2263 (2017) |
Popis: | 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. |
Databáze: | OpenAIRE |
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