Reply to the ‘Comment on “Cholesterol Solubility Limit in Lipid Membranes probed by Small Angle Neutron Scattering and MD simulations”’ by R. Epand, Soft Matter, 2015, 11, DOI: 10.1039/C4SM02819H

Krzyzanowski, Natalie; Porcar, Lionel; Garg, Sumit; Butler, Paul; Castro-Roman, Francisco; Bautista, Pedro Jesus; Perez-Salas, Ursula

doi:10.1039/c5sm01071c

Cited by 4 publications

(3 citation statements)

References 17 publications

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“…More recently, we found how defects in membrane packing induced by a supporting surface facilitate lipid flip-flop too and methodologies that can potentially have this effect on membranes result in inaccurate measured rates ( 39 ). From the MD side, we have also suggested that the tendency of the simulations to accumulate cholesterol in the bilayer center suggests that the energy barrier to flip is too low ( 46 , 47 ). Further, with TR-SANS, we have demonstrated that although exchange and flip-flop are coupled, it is their interdependence in the movement of lipids between and within membranes that allows for their distinction, even when the most significant contribution in TR-SANS comes from the exchange process as supported by the AIC test.…”

Section: Discussionmentioning

confidence: 94%

Influence of the membrane environment on cholesterol transfer

Breidigan

Krzyzanowski

Liu

et al. 2017

Journal of Lipid Research

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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.

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Section: Discussionmentioning

confidence: 94%

Influence of the membrane environment on cholesterol transfer

Breidigan

Krzyzanowski

Liu

et al. 2017

Journal of Lipid Research

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“…In particular, while it is known that the pseudobilayer periodicity (34 Å) of cholesterol can only be readily detected by X-ray diffraction upon cholesterol phase separation in multi-lamellar vesicles, 3 the authors look for it in an X-ray diffraction pattern from a sample of unilamellar phospholipid/ cholesterol vesicles (ref. 1 and Fig. 1A).…”

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confidence: 79%

“…As authors of the ''Comment on 'Cholesterol solubility limit in lipid membranes probed by small angle neutron scattering and MD simulations''', we wish to comment on both the form and content of the Reply cited above. 1 In their original article, 2 Garg et al used neutron scattering techniques to determine the limiting amount of cholesterol which vesicles of either POPS or POPC can accommodate. They called this amount ''the cholesterol solubility limit''.…”

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confidence: 99%