CoChat
Sign Up
Cited by 136Lipid Membrane Structure and BehaviorCaveolin-1 and cellular processesMembrane Separation and Gas Transport

Permeability of membranes in the liquid ordered and liquid disordered phases

Open access
Ghysels, An, Krämer, Andreas, Venable, Richard M., Teague, Walter E., Lyman, Edward, Gawrisch, Klaus, Pastor, Richard W.·2019·Nature Communications
DOI 10.1038/s41467-019-13432-7PMC PMC6901538
Open this paper in CoChat — free accountOpen PDF

Abstract

The functional significance of ordered nanodomains (or rafts) in cholesterol rich eukaryotic cell membranes has only begun to be explored. This study exploits the correspondence of cellular rafts and liquid ordered ( L o ) phases of three-component lipid bilayers to examine permeability. Molecular dynamics simulations of L o phase dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylcholine (DOPC), and cholesterol show that oxygen and water transit a leaflet through the DOPC and cholesterol rich boundaries of hexagonally packed DPPC microdomains, freely diffuse along the bilayer midplane, and escape the membrane along the boundary regions. Electron paramagnetic resonance experiments provide critical validation: the measured ratio of oxygen concentrations near the midplanes of liquid disordered ( L d ) and L o bilayers of DPPC/DOPC/cholesterol is 1.75 ± 0.35, in very good agreement with 1.3 ± 0.3 obtained from simulation. The results show how cellular rafts can be structurally rigid signaling platforms while remaining nearly as permeable to small molecules as the L d phase.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41467-019-13432-7

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • GUVs are established models for lipid bilayer membranes, emulating cell membranes to some extent.

    “To validate our mechanism of electropore-facilitated membrane fusion, we examined the interactions of GUVs, which are established models for lipid bilayer membranes 41,42 , emulating cell membranes to some extent.”

    From Fusion of lipid membranes: an alternative pathway (2026) · cites this paper as [42]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 56

  1. [1]Simons K Ikonen E Functional rafts in cell membranes Nature 1997 387 569 572 10.1038/42408 9177342 · DOI · Paper page
  2. [2]Sezgin E Levental I Mayor S Eggeling C The mystery of membrane organization: composition, regulation and roles of lipid rafts Nat. Rev. Mol. Cell Biol. 2017 18 361 374 10.1038/nrm.2017.16 28356571 PMC5500228 · DOI · Paper page
  3. [3]Dietrich C Lipid rafts reconstituted in model membranes Biophys. J. 2001 80 1417 1428 10.1016/S0006-3495(01)76114-0 11222302 PMC1301333 · DOI
  4. [4]Samsonov AV Mihalyov I Cohen FS Characterization of cholesterol-sphingomyelin domains and their dynamics in bilayer membranes Biophys. J. 2001 81 1486 1500 10.1016/S0006-3495(01)75803-1 11509362 PMC1301627 · DOI
  5. [5]Munro S Lipid rafts: elusive or illusive? Cell 2003 115 377 388 10.1016/S0092-8674(03)00882-1 14622593 · DOI
  6. [6]Baumgart T Large-scale fluid/fluid phase separation of proteins and lipids in giant plasma membrane vesicles Proc. Natl Acad. Sci. USA 2007 104 3165 3170 10.1073/pnas.0611357104 17360623 PMC1805587 · DOI
  7. [7]Sezgin Erdinc Gutmann Theresia Buhl Tomasz Dirkx Ron Grzybek Michal Coskun Ünal Solimena Michele Simons Kai Levental Ilya Schwille Petra Adaptive Lipid Packing and Bioactivity in Membrane Domains PLOS ONE 2015 10 4 e0123930 10.1371/journal.pone.0123930 25905447 PMC4408024 · DOI
  8. [8]Eggeling C Direct observation of the nanoscale dynamics of membrane lipids in a living cell Nature 2009 457 1159 U1121 10.1038/nature07596 19098897 · DOI
  9. [9]Stone, M. B., Shelby, S. A., Nunez, M. F., Wisser, K. & Veatch, S. L. Protein sorting by lipid phase-like domains supports emergent signaling function in B lymphocyte plasma membranes. eLife6, e19891 (2017). PMC5373823 28145867
  10. [10]Venable R Krämer A Pastor RW Molecular dynamics simulations of membrane permeability Chem. Rev. 2019 119 5954 5997 10.1021/acs.chemrev.8b00486 30747524 PMC6506413 · DOI
  11. [11]Ghysels A Venable RM Pastor RW Hummer G Position-dependent diffusion tensors in anisotropic media from simulation: oxygen transport in and through membranes J. Chem. Theory Comput. 2017 13 2962 2976 10.1021/acs.jctc.7b00039 28482659 PMC6311093 · DOI
  12. [12]De Vos A Membrane permeability: characteristic times and lengths for oxygen, and a simulation-based test of the inhomogeneous solubility-diffusion model J. Chem. Theory Comput. 2018 14 3811 3824 10.1021/acs.jctc.8b00115 29894626 PMC6295149 · DOI
  13. [13]De Vos, O., Van Hecke, T. & Ghysels, A. In Oxygen Transport to Tissue Xl, Vol. 1072 Advances in Experimental Medicine and Biology (eds Thews, O., LaManna, J. C. & Harrison, D. K.) 399–404 (Springer, London, 2018). 31586355
  14. [14]Dotson RJ Smith CR Bueche K Angles G Pias SC Influence of cholesterol on the oxygen permeability of membranes: insight from atomistic simulations Biophys. J. 2017 112 2336 2347 10.1016/j.bpj.2017.04.046 28591606 PMC5474842 · DOI
  15. [15]Van der Paal J Verheyen C Neyts EC Bogaerts A Hampering effect of cholesterol on the permeation of reactive oxygen species through phospholipids bilayer: possible explanation for plasma cancer selectivity Sci. Rep. 2017 7 39526 10.1038/srep39526 28059085 PMC5216346 · DOI
  16. [16]Plesnar E Szczelina R Subczynski WK Pasenkiewicz-Gierula M Is the cholesterol bilayer domain a barrier to oxygen transport into the eye lens? BBA-Biomembranes 2018 1860 434 441 10.1016/j.bbamem.2017.10.020 29079282 PMC5732854 · DOI
  17. [17]Sajadi F Rowley CN Simulations of lipid bilayers using the CHARMM36 force field with the TIP3P-FB and TIP4P-FB water models PeerJ 2018 6 e5472 10.7717/peerj.5472 30128211 PMC6097494 · DOI
  18. [18]Krämer A Interactions of water and alkanes: modifying additive force fields to account for polarization effects J. Chem. Theory Comput. 2019 15 3854 3867 10.1021/acs.jctc.9b00016 31002505 PMC6602074 · DOI
  19. [19]Hyde, J. S. & Subczynski, W. K. In Biological Magnetic Resonance. Vol. 8 Spin Labeling – Theory and Applications (Bernlinger, L. J. & Reuben, J.) 399–425 (Plenum Press, New York and London, 1989).
  20. [20]Dzikovski BG Livshits VA Marsh D Oxygen permeation profile in lipid membranes: comparison with transmembrane polarity profile Biophys. J. 2003 85 1005 1012 10.1016/S0006-3495(03)74539-1 12885647 PMC1303221 · DOI
  21. [21]Altenbach C Greenhalgh DA Khorana HG Hubbell WL A collision gradient-method to determine the immersion depth of nitrozides in lipid bilayers—application to spin-labelled mutants of bacteriorhodopsin Proc. Natl Acad. Sci. USA 1994 91 1667 1671 10.1073/pnas.91.5.1667 8127863 PMC43224 · DOI
  22. [22]Oh, K. J., Altenebach, C., Collier, R. J. & Hubbell, W. L. In Bacterial Toxins: Methods and Protocols. Vol. 145 (ed. Holst, O.) 147–168 (Humana Press Inc., 2000).
  23. [23]Subczynski WK Hyde JS Kusumi A Oxygen permeability of phosphatidylcholine cholesterol membranes Proc. Natl Acad. Sci. USA 1989 86 4474 4478 10.1073/pnas.86.12.4474 2543978 PMC287292 · DOI
  24. [24]Guler SD Effects of ether vs. ester linkage on lipid bilayer structure and water permeability Chem. Phys. Lipids 2009 160 33 44 10.1016/j.chemphyslip.2009.04.003 19416724 PMC2698298 · DOI
  25. [25]Sodt AJ Sandar ML Gawrisch K Pastor RW Lyman E The molecular structure of the liquid ordered phase of lipid bilayers J. Am. Chem. Soc. 2014 136 725 732 10.1021/ja4105667 24345334 PMC4197129 · DOI
  26. [26]Veatch SL Soubias O Keller SL Gawrisch K Critical fluctuations in domain-forming lipid mixtures Proc. Natl Acad. Sci. USA 2007 104 17650 17655 10.1073/pnas.0703513104 17962417 PMC2077022 · DOI
  27. [27]Wu H-M Lin Y-H Yen T-C Hsieh C-L Nanoscopic substructures of raft-mimetic liquid ordered membrane domains revealed by high-speed single-particle tracking Sci. Rep. 2016 6 20542 10.1038/srep20542 26861908 PMC4997016 · DOI
  28. [28]Sodt AJ Pastor RW Lyman E Hexagonal substructure and hydrogen bonding in liquid ordered phases containing palmitoyl sphingomyelin Biophys. J. 2015 109 948 955 10.1016/j.bpj.2015.07.036 26331252 PMC4564825 · DOI
  29. [29]Mathai JC Tristram-Nagle S Nagle JF Zeidel ML Structural determinants of water permeability through the lipid membrane J. Gen. Physiol. 2008 131 69 76 10.1085/jgp.200709848 18166626 PMC2174160 · DOI
  30. [30]Shaw DE Anton, a special-purpose machine for molecular dynamics simulation Comm. ACM 2008 51 91 97 10.1145/1364782.1364802 · DOI
  31. [31]Windrem DA Plachy WZ The diffusion-solubility of oxygen in lipid bilayers BBA-Biomembranes 1980 600 655 665 10.1016/0005-2736(80)90469-1 6250601 · DOI
  32. [32]Yang LW Kindt JT Simulation study of the permeability of a model lipid membrane at the fluid solid phase transition Langmuir 2015 31 2187 2195 10.1021/la504269t 25621817 · DOI
  33. [33]Yang LW Kindt JT Line tension assists membrane permeation at the transition temperature in mixed-phase lipid bilayers J. Phys. Chem. B 2016 120 11740 11750 10.1021/acs.jpcb.6b06690 27780354 · DOI
  34. [34]Cordeiro RM Molecular structure and permeability at the interface between phase-separated membrane domains J. Phys. Chem. B 2018 122 6954 6965 10.1021/acs.jpcb.8b03406 29767519 · DOI
  35. [35]Del Regno A Notman R Permeation pathways through lateral domains in model membranes of skin lipids Phys. Chem. Chem. Phys. 2018 20 2162 2174 10.1039/C7CP03258G 29116267 · DOI
  36. [36]Nagle JF Mathai JC Zeidel ML Tristram-Nagle S Theory of passive permeability through lipid bilayers J. Gen. Physiol. 2008 131 77 85 10.1085/jgp.200709849 18166627 PMC2174158 · DOI
  37. [37]Guixà-González R MEMBPLUGIN: studying membrane complexity in VMD Bioinformatics 2014 30 1478 1480 10.1093/bioinformatics/btu037 24451625 · DOI
  38. [38]Venable RM Brown FLH Pastor RW Mechanical properties of lipid bilayers from molecular dynamics simulation Chem. Phys. Lipids 2015 192 60 74 10.1016/j.chemphyslip.2015.07.014 26238099 PMC4684433 · DOI
  39. [39]Sun WJ TristramNagle S Suter RM Nagle JF Structure of gel phase saturated lecithin bilayers: Temperature and chain length dependence Biophys. J. 1996 71 885 891 10.1016/S0006-3495(96)79290-1 8842227 PMC1233545 · DOI
  40. [40]Nagle JF Cognet P Dupuy FG Tristram-Nagle S Structure of gel phase DPPC determined by X-ray diffraction Chem. Phys. Lipids 2019 218 168 177 10.1016/j.chemphyslip.2018.12.011 30593772 · DOI
  41. [41]Golebiewska U Evidence for a fence that impedes the diffusion of phosphatidylinositol 4,5-bisphosphate out of the forming phagosomes of macrophages Mol. Biol. Cell 2011 22 3498 3507 10.1091/mbc.e11-02-0114 21795401 PMC3172273 · DOI
  42. [42]Lee, K. I., Im, W. & Pastor, R. W. Langevin dynamics simulations of charged model phosphatidylinositol lipids in the presence of diffusion barriers: toward an atomic level understanding of corralling of PIP2 by protein fences in biological membranes. BmcBiophysics7, 13 (2014). PMC4358915 25774289
  43. [43]Möller MN Solubility and diffusion of oxygen in phospholipid membranes BBA-Biomembranes 2016 1858 2923 2930 10.1016/j.bbamem.2016.09.003 27614191 · DOI
  44. [44]Bacellar IOL Oxygen distribution in the fluid/gel phases of lipid membranes BBA-Biomembranes 2019 1861 879 886 10.1016/j.bbamem.2019.01.019 30716292 · DOI
  45. [45]Hjort Ipsen J Karlström G Mourtisen OG Wennerström H Zuckermann MJ Phase equilibria in the phosphatidylcholine-cholesterol system BBA-Biomembranes 1987 905 162 172 10.1016/0005-2736(87)90020-4 3676307 · DOI
  46. [46]Widomska J Raguz M Subczynski WK Oxygen permeability of the lipid bilayer membrane made of calf lens lipids BBA-Biomembranes 2007 1768 2635 2645 10.1016/j.bbamem.2007.06.018 17662231 PMC2093700 · DOI
  47. [47]Moller M Direct measurement of nitric oxide and oxygen partitioning into liposomes and low density lipoprotein J. Biol. Chem. 2005 280 8850 8854 10.1074/jbc.M413699200 15632138 · DOI
  48. [48]Jakobtorweihen S. Zuniga A. Chaides Ingram T. Gerlach T. Keil F. J. Smirnova I. Predicting solute partitioning in lipid bilayers: Free energies and partition coefficients from molecular dynamics simulations and COSMOmic The Journal of Chemical Physics 2014 141 4 045102 10.1063/1.4890877 25084963 · DOI
  49. [49]Petersen, E. N., Chung, H. W., Nayebosadri, A. & Hansen, S. B. Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D. Nat. Commun. 7, 13873 (2016). PMC5171650 27976674
  50. [50]Pavel, M. A., Petersen, E. N., Lerner, R. A. & Hansen, S. B. Studies on the mechanism of general anesthesia. Preprint at 10.1101/313973 (2018). PMC7306821 32467161 · DOI
  51. [51]Brooks BR CHARMM: the biomolecular simulation program J. Comput. Chem. 2009 30 1545 1614 10.1002/jcc.21287 19444816 PMC2810661 · DOI
  52. [52]Klauda JB Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types J. Phys. Chem. B 2010 114 7830 7843 10.1021/jp101759q 20496934 PMC2922408 · DOI
  53. [53]de Groot BL Tieleman DP Pohl P Grubmüller H Water permeation through gramicidin a: desformylation and the double helix: a molecular dynamics study Biophys. J. 2002 82 2934 2942 10.1016/S0006-3495(02)75634-8 12023216 PMC1302081 · DOI
  54. [54]Hub JS de Groot BL Does CO2 permeate through aquaporin-1? Biophys. J. 2006 91 842 848 10.1529/biophysj.106.081406 16698771 PMC1563782 · DOI
  55. [55]Diamond JM Katz Y Interpretation of nonelectrolyte partition-coefficients bewteen dimyristroyl lecithin and water J. Membr. Biol. 1974 17 121 154 10.1007/BF01870176 4407798 · DOI
  56. [56]Mostofian B Zuckerman DM Statistical uncertainty analysis for small-sample, high log-variance data: cautions for bootstrapping and bayesian bootstrapping J. Chem. Theory Comput. 2019 15 3499 3509 10.1021/acs.jctc.9b00015 31002504 PMC6754704 · DOI

Cited by

Sorted by citations

Authors
Ghysels, A., Krämer, A., Venable, R. M., Teague, W. E., Lyman, E., Gawrisch, K., & Pastor, R. W.
Affiliations
  • Ghent University (BE)
  • National Institutes of Health (US)
  • University of Delaware (US)
Corresponding author
  • Ghysels, An
  • Pastor, Richard W.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2019-12-09
Volume
10
Issue
1
Pages
5616-5616
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-019-13432-7
PMC
PMC6901538
OpenAlex
W2991711788
Cited by
136
References
0
Citations by year
2026: 14 · 2025: 20 · 2024: 30 · 2023: 22 · 2022: 18 · 2021: 21 · 2020: 11
FWCI
4.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Vlaams Supercomputer Centrum
  • Fonds Wetenschappelijk Onderzoek
  • Universiteit Gent
  • Vlaamse regering
  • National Institutes of Health (NIH-R01)
  • National Institute on Alcohol Abuse and Alcoholism
  • National Heart, Lung, and Blood Institute (NIH R01)
  • National Institute of General Medical Sciences (R01GM120351, R01GM116961)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
  • Physical Sciences › Engineering › Mechanical Engineering › Membrane Separation and Gas Transport
Keywords
membrane permeability, liquid-ordered phase, liquid-disordered phase, lipid rafts, cholesterol, DPPC, DOPC, oxygen diffusion, water diffusion, lipid bilayers, microdomains, electron spin resonance, molecular dynamics simulation
MeSH terms
Cell Membrane Permeability, Cholesterol, Computer Simulation, Diffusion, Lipid Bilayers, Oxygen, Phosphatidylcholines, Probability, Thermodynamics, 1,2-Dipalmitoylphosphatidylcholine

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review