Interdigitation of long-chain sphingomyelin induces coupling of membrane leaflets in a cholesterol dependent manner

Tomasz Róg; Adam Orłowski; Alicia Llorente; Tore Skotland; Tuulia Sylvänne; Dimple Kauhanen; Kim Ekroos; Kirsten Sandvig; Ilpo Vattulainen

doi:10.1016/j.bbamem.2015.12.003

Interdigitation of long-chain sphingomyelin induces coupling of membrane leaflets in a cholesterol dependent manner

Biochim Biophys Acta. 2016 Feb;1858(2):281-8. doi: 10.1016/j.bbamem.2015.12.003. Epub 2015 Dec 2.

Authors

Tomasz Róg¹, Adam Orłowski², Alicia Llorente³, Tore Skotland³, Tuulia Sylvänne⁴, Dimple Kauhanen⁴, Kim Ekroos⁴, Kirsten Sandvig⁵, Ilpo Vattulainen⁶

Affiliations

¹ Department of Physics, Tampere University of Technology, P. O. Box 692, FI-33101 Tampere, Finland.
² Department of Physics, Tampere University of Technology, P. O. Box 692, FI-33101 Tampere, Finland; Department of Physics and Energy, University of Limerick, Limerick, Ireland.
³ Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, 0316 Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, 0316 Oslo, Norway.
⁴ Zora Biosciences Oy, 02150 Espoo, Finland.
⁵ Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, 0316 Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, 0316 Oslo, Norway; Department of Biosciences, University of Oslo, 0316 Oslo, Norway.
⁶ Department of Physics, Tampere University of Technology, P. O. Box 692, FI-33101 Tampere, Finland; MEMPHYS - Center for Biomembrane Physics, University of Southern Denmark, Odense, Denmark; Department of Physics, University of Helsinki, P.O. Box 43, FI-00014 Helsinki, Finland. Electronic address: Ilpo.Vattulainen@tut.fi.

PMID: 26654782
DOI: 10.1016/j.bbamem.2015.12.003

Abstract

It has been a long-standing question how the two leaflets in a lipid bilayer modulate each others' physical properties. In this paper, we discuss how this interaction may take place through interdigitation. We use atomistic molecular dynamics simulations to consider asymmetric lipid membrane models whose compositions are based on the lipidomics data determined for exosomes released by PC-3 prostate cancer cells. The simulations show interdigitation to be exceptionally strong for long-chain sphingomyelin (SM) molecules. In asymmetric membranes the amide-linked chain of SM is observed to extend deep into the opposing membrane leaflet. Interestingly, we find that the conformational order of the amide-linked SM chain increases the deeper it penetrates to the opposing leaflet. Analysis of this finding reveals that the amide-linked SM chain interacts favorably with the lipid chains in the opposite leaflet, and that cholesterol modulates the effect of SM interdigitation by influencing the conformational order of lipid hydrocarbon chains in the opposing (cytosolic) leaflet.

Keywords: Cholesterol; Computer simulation; Exosome; Interdigitation; Lipid membrane; Lipidomics; Molecular dynamics simulation; Sphingomyelin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Membrane / metabolism*
Cholesterol / metabolism*
Humans
Male
Models, Biological*
Prostatic Neoplasms / metabolism*
Sphingomyelins / metabolism*

Substances

Sphingomyelins
Cholesterol