Long-chain GM1 gangliosides alter transmembrane domain registration through interdigitation

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. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

Atomistic Fingerprint of Hyaluronan-CD44 Binding: Weak E-field Simulations, Upright Mode

Simulation files (Gromacs 4.6.7 format) for the "E-field weak, upright mode" simulations in Ref. [1]. There are 20 replicas marked with "_1" , "_2", etc. Files include: -trajectories (.xtc) that are saved every 100ps -initial structures (.gro), -run input files (.tpr) -checkpoint files (.cpt) -simulation parameter files (.mdp) -system topology file (.top) -topology files included in the system topology file (.itp) [1] Vuorio J. et al., Atomistic Fingerprint of Hyaluronan-CD44 Binding, PLOS Comp. Biol., 2017. (Submitted

Atomistic Fingerprint of Hyaluronan-CD44 Binding: Clustering Simulations

Simulation files (Gromacs 4.6.7 format) for the "Clustering" simulations in Ref. [1]. There are two replicas marked with "_1" and "_2". Files include: -trajectories (.xtc) that are saved every 100ps -initial structures (.gro), -run input files (.tpr) -checkpoint files (.cpt) -simulation parameter files (.mdp) -system topology file (.top) -topology files included in the system topology file (.itp) [1] Vuorio J. et al., Atomistic Fingerprint of Hyaluronan-CD44 Binding, PLOS Comp. Biol., 2017. (Submitted

Atomistic Fingerprint of Hyaluronan-CD44 Binding: Weak E-field Simulations, Crystallographic Mode

Simulation files (Gromacs 4.6.7 format) for the "E-field weak, crystallographic mode" simulations in Ref. [1]. There are 20 replicas marked with "_1" , "_2", etc. Files include: -trajectories (.xtc) that are saved every 100ps -initial structures (.gro), -run input files (.tpr) -checkpoint files (.cpt) -simulation parameter files (.mdp) -system topology file (.top) -topology files included in the system topology file (.itp) [1] Vuorio J. et al., Atomistic Fingerprint of Hyaluronan-CD44 Binding, PLOS Comp. Biol., 2017. (Submitted

Atomistic Fingerprint of Hyaluronan-CD44 Binding: Weak E-field Simulations, Parallel Mode

<p>Simulation files (Gromacs 4.6.7 format) for the "E-field weak, parallel mode" simulations in Ref. [1]. There are 20 replicas marked with "_1" , "_2", etc.</p> <p>Files include:</p> <p>-trajectories (.xtc) that are saved every 100ps <br> -initial structures (.gro), <br> -run input files (.tpr)<br> -checkpoint files (.cpt)<br> -simulation parameter files (.mdp)<br> -system topology file (.top)<br> -topology files included in the system topology file (.itp)</p> <p>[1] Vuorio J. et al., Atomistic Fingerprint of Hyaluronan-CD44 Binding, PLOS Comp. Biol., 2017. (Submitted)</p

The Key Role of Temperature and Lipid Composition in Modulating the Intake of Gold Nanoparticles into the Plasma Membrane

International audienceMonolayer-protected gold nanoparticles are emerging as promising candidates for drug delivery due to their ability to permeate through plasma membranes. Understanding the molecular mechanisms of such complex systems is crucial to control cell permeation and to develop efficient biomedical delivery applications based on nanoscale gold nanoparticles. Here, neutron reflectometry (NR) and molecular dynamics (MD) simulations were used to shed light on the interaction between cationic gold nanoparticles (AuNPs) and model lipid membranes and the consequences thereof. Atomistic simulations predicted that there is a free energy barrier that has to be overcome to enforce AuNPs to partition into a DSPC bilayer. NR experiments confirmed the prediction, showing that AuNP encapsulation takes place only at temperatures higher than ∼330 K. Meanwhile, in a mixture of DSPC-DSPG (3:1), experiments showed that the adsorption of AuNPs to the membrane is weak; the nanoparticles were readily released during annealing. Coarse-grained MD simulations used to interpret this behaviour indicated that in this mixture DSPGs migrate around AuNPs, thereby weakening their interaction with the surface and leading to detachment of AuNPs at high temperatures. NR experiments also confirmed this by showing that in the presence of negative lipids (DSPG), desorption of AuNPs is associated with a reduced coverage of the floating bilayer, suggesting that some lipids, which comprise both DSPC and DSPG, are extracted and left the bilayer. Finally, the results indicated that the crowding of lipids over the nanoparticles shields the electrostatic interaction between cationic nanoparticles, thus fostering their aggregation on the membrane surface and driving the membrane composition to be locally asymmetric, causing membrane instability