Cholesterol Flip-Flop Impacts Domain Registration in Plasma Membrane Models

Overview

Journal J Phys Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2018 Sep 8

PMID 30192549

Citations 17

Authors

Sebastian Thallmair

Helgi I Ingolfsson

Siewert J Marrink

Affiliations

Soon will be listed here.

Abstract

The plasma membrane is a highly complex multicomponent system that is central to the functioning of cells. Cholesterol, a key lipid component of the plasma membrane, promotes the formation of nanodomains. These nanodomains are often correlated across the two membrane leaflets, but the underlying physical mechanism remains unclear. Using coarse-grained molecular dynamics simulations, we investigate the influence of cholesterol flip-flop on membrane properties, in particular, the interleaflet coupling of cholesterol-enriched domains. We show that the cholesterol density correlation between the leaflets of an average mammalian plasma membrane is significantly reduced by suppressing interleaflet cholesterol population. Our results suggest an amplifying role of cholesterol in signal transduction across the leaflets.

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References

Lin X, Zhang S, Ding H, Levental I, Gorfe A . The aliphatic chain of cholesterol modulates bilayer interleaflet coupling and domain registration. FEBS Lett. 2016; 590(19):3368-3374. PMC: 5064870. DOI: 10.1002/1873-3468.12383. View

Risselada H, Marrink S . The molecular face of lipid rafts in model membranes. Proc Natl Acad Sci U S A. 2008; 105(45):17367-72. PMC: 2579886. DOI: 10.1073/pnas.0807527105. View

Fowler P, Williamson J, Sansom M, Olmsted P . Roles of Interleaflet Coupling and Hydrophobic Mismatch in Lipid Membrane Phase-Separation Kinetics. J Am Chem Soc. 2016; 138(36):11633-42. PMC: 5025830. DOI: 10.1021/jacs.6b04880. View

Manna M, Javanainen M, Monne H, Gabius H, Rog T, Vattulainen I . Long-chain GM1 gangliosides alter transmembrane domain registration through interdigitation. Biochim Biophys Acta Biomembr. 2017; 1859(5):870-878. DOI: 10.1016/j.bbamem.2017.01.033. View

Levental I, Grzybek M, Simons K . Raft domains of variable properties and compositions in plasma membrane vesicles. Proc Natl Acad Sci U S A. 2011; 108(28):11411-6. PMC: 3136254. DOI: 10.1073/pnas.1105996108. View

Marrink S, De Vries A, Harroun T, Katsaras J, Wassall S . Cholesterol shows preference for the interior of polyunsaturated lipid membranes. J Am Chem Soc. 2007; 130(1):10-1. DOI: 10.1021/ja076641c. View

Ingolfsson H, Melo M, van Eerden F, Arnarez C, Lopez C, Wassenaar T . Lipid organization of the plasma membrane. J Am Chem Soc. 2014; 136(41):14554-9. DOI: 10.1021/ja507832e. View

Kiessling V, Wan C, Tamm L . Domain coupling in asymmetric lipid bilayers. Biochim Biophys Acta. 2008; 1788(1):64-71. PMC: 3099438. DOI: 10.1016/j.bbamem.2008.09.003. View

Corradi V, Mendez-Villuendas E, Ingolfsson H, Gu R, Siuda I, Melo M . Lipid-Protein Interactions Are Unique Fingerprints for Membrane Proteins. ACS Cent Sci. 2018; 4(6):709-717. PMC: 6028153. DOI: 10.1021/acscentsci.8b00143. View

10.

Zhao J, Wu J, Heberle F, Mills T, Klawitter P, Huang G . Phase studies of model biomembranes: complex behavior of DSPC/DOPC/cholesterol. Biochim Biophys Acta. 2007; 1768(11):2764-76. PMC: 2701629. DOI: 10.1016/j.bbamem.2007.07.008. View

11.

Baumgart T, Hess S, Webb W . Imaging coexisting fluid domains in biomembrane models coupling curvature and line tension. Nature. 2003; 425(6960):821-4. DOI: 10.1038/nature02013. View

12.

Galimzyanov T, Kuzmin P, Pohl P, Akimov S . Undulations Drive Domain Registration from the Two Membrane Leaflets. Biophys J. 2017; 112(2):339-345. PMC: 5266264. DOI: 10.1016/j.bpj.2016.12.023. View

13.

Weiner M, Feigenson G . Presence and Role of Midplane Cholesterol in Lipid Bilayers Containing Registered or Antiregistered Phase Domains. J Phys Chem B. 2018; 122(34):8193-8200. DOI: 10.1021/acs.jpcb.8b03949. View

14.

Harayama T, Riezman H . Understanding the diversity of membrane lipid composition. Nat Rev Mol Cell Biol. 2018; 19(5):281-296. DOI: 10.1038/nrm.2017.138. View

15.

Belicka M, Weitzer A, Pabst G . High-resolution structure of coexisting nanoscopic and microscopic lipid domains. Soft Matter. 2017; 13(9):1823-1833. DOI: 10.1039/c6sm02727j. View

16.

Bennett W, MacCallum J, Hinner M, Marrink S, Tieleman D . Molecular view of cholesterol flip-flop and chemical potential in different membrane environments. J Am Chem Soc. 2009; 131(35):12714-20. DOI: 10.1021/ja903529f. View

17.

Veatch S, Cicuta P, Sengupta P, Honerkamp-Smith A, Holowka D, Baird B . Critical fluctuations in plasma membrane vesicles. ACS Chem Biol. 2008; 3(5):287-93. DOI: 10.1021/cb800012x. View

18.

Reigada R . Alteration of interleaflet coupling due to compounds displaying rapid translocation in lipid membranes. Sci Rep. 2016; 6:32934. PMC: 5011781. DOI: 10.1038/srep32934. View

19.

Eicher B, Marquardt D, Heberle F, Letofsky-Papst I, Rechberger G, Appavou M . Intrinsic Curvature-Mediated Transbilayer Coupling in Asymmetric Lipid Vesicles. Biophys J. 2018; 114(1):146-157. PMC: 5773765. DOI: 10.1016/j.bpj.2017.11.009. View

20.

Jo S, Rui H, Lim J, Klauda J, Im W . Cholesterol flip-flop: insights from free energy simulation studies. J Phys Chem B. 2010; 114(42):13342-8. DOI: 10.1021/jp108166k. View