title: Long-chain GM1 gangliosides alter transmembrane domain registration through interdigitation.
abstract: Extracellular and cytosolic leaflets in cellular membranes are distinctly different in lipid composition, yet they contribute together to signaling across the membranes. Here we consider a mechanism based on long-chain gangliosides for coupling the extracellular and cytosolic membrane leaflets together. Based on atomistic molecular dynamics simulations, we find that long-chain GM1 in the extracellular leaflet exhibits a strong tendency to protrude into the opposing bilayer leaflet. This interdigitation modulates the order in the cytosolic monolayer and thereby strengthens the interaction and coupling across a membrane. Coarse-grained simulations probing longer time scales in large membrane systems indicate that GM1 in the extracellular leaflet modulates the phase behavior in the cytosolic monolayer. While short-chain GM1 maintains phase-symmetric bilayers with a strong membrane registration effect, the situation is altered with long-chain GM1. Here, the significant interdigitation induced by long-chain GM1 modulates the behavior in the cytosolic GM1-free leaflet, weakening and slowing down the membrane registration process. The observed physical interaction mechanism provides a possible means to mediate or foster transmembrane communication associated with signal transduction.
authors.affiliation: Department of Physics, Tampere University of Technology, P. O. Box 692, FI- 33101 Tampere, Finland.
authors.forename: Moutusi
authors.initials: M
authors.lastname: Manna
authors.affiliation: Department of Physics, Tampere University of Technology, P. O. Box 692, FI- 33101 Tampere, Finland; Department of Physics, POB 64, FI-00014 University of Helsinki, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Javanainen
authors.affiliation: Department of Physics, Tampere University of Technology, P. O. Box 692, FI- 33101 Tampere, Finland; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, CZ-16610, Prague, Czech Republic.
authors.forename: Hector Martinez-Seara
authors.initials: HM
authors.lastname: Monne
authors.affiliation: Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig Maximilian University, D-80539 Munchen, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gabius
authors.affiliation: Department of Physics, Tampere University of Technology, P. O. Box 692, FI- 33101 Tampere, Finland; Department of Physics, POB 64, FI-00014 University of Helsinki, Finland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Rog
authors.affiliation: Department of Physics, Tampere University of Technology, P. O. Box 692, FI- 33101 Tampere, Finland; Department of Physics, POB 64, FI-00014 University of Helsinki, Finland; MEMPHYS-Center for Biomembrane Physics, University of Southern Denmark, Odense, Denmark. Electronic address: Ilpo.Vattulainen@helsinki.fi.
authors.forename: Ilpo
authors.initials: I
authors.lastname: Vattulainen
mesh_terms: D005677:G(M1) Ganglioside / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation
chemical_list: D008051:Lipid Bilayers; D005677:G(M1) Ganglioside
keywords: Glycosphingolipid; cholesterol; computer simulations; membrane domain; membrane registry; molecular dynamics