Desipramine induces disorder in cholesterol-rich membranes:implications for viral trafficking

In this study, the effect of desipramine (DMI) on phospholipid bilayers and parvoviral entry was elucidated. In atomistic molecular dynamics simulations, DMI was found to introduce disorder in cholesterol-rich phospholipid bilayers. This was manifested by a decrease in the deuterium order parameter S(CD) as well as an increase in the membrane area. Disordering of the membrane suggested DMI to destabilize cholesterol-rich membrane domains (rafts) in cellular conditions. To relate the raft disrupting ability of DMI with novel biological relevance, we studied the intracellular effect of DMI using canine parvovirus (CPV), a virus known to interact with endosomal membranes and sphingomyelin, as …

Psychedelics promote plasticity by directly binding to BDNF receptor TrkB

10 paginas, 15 fguras

Cationic Au Nanoparticle Binding with Plasma Membrane-like Lipid Bilayers: Potential Mechanism for Spontaneous Permeation to Cells Revealed by Atomistic Simulations

Despite being chemically inert as a bulk material, nanoscale gold can pose harmful side effects to living organisms. In particular, cationic Au nanoparticles (AuNP+) of 2 nm diameter or less permeate readily through plasma membranes and induce cell death. We report atomistic simulations of cationic Au nanoparticles interacting with realistic membranes and explicit solvent using a model system that comprises two cellular compartments, extracellular and cytosolic, divided by two asymmetric lipid bilayers. The membrane-AuNP+ binding and membrane reorganization processes are discovered to be governed by cooperative effects where AuNP+, counterions, water, and the two membrane leaflets all contr…

The role of hydrophobic matching on transmembrane helix packing in cells

Folding and packing of membrane proteins are highly influenced by the lipidic component of the membrane. Here, we explore how the hydrophobic mismatch (the difference between the hydrophobic span of a transmembrane protein region and the hydrophobic thickness of the lipid membrane around the protein) influences transmembrane helix packing in a cellular environment. Using a ToxRED assay in Escherichia coli and a Bimolecular Fluorescent Complementation approach in human-derived cells complemented by atomistic molecular dynamics simulations we analyzed the dimerization of Glycophorin A derived transmembrane segments. We concluded that, biological membranes can accommodate transmembrane homo-di…

N- and O-methylation of sphingomyelin markedly affects its membrane properties and interactions with cholesterol

We have prepared palmitoyl sphingomyelin (PSM) analogs in which either the 2-NH was methylated to NMe, the 3-OH was methylated to OMe, or both were methylated simultaneously. The aim of the study was to determine how such modifications in the membrane interfacial region of the molecules affected interlipid interactions in bilayer membranes. Measuring DPH anisotropy in vesicle membranes prepared from the SM analogs, we observed that methylation decreased gel-phase stability and increased fluid phase disorder, when compared to PSM. Methylation of the 2-NH had the largest effect on gel-phase instability (T(m), was lowered by similar to 7 degrees C). Atomistic molecular dynamics simulations sho…

Negatively Charged Gangliosides Promote Membrane Association of Amphipathic Neurotransmitters

Lipophilic neurotransmitters (NTs) such as dopamine are chemical messengers enabling neurotransmission by adhering onto the extracellular surface of the post-synaptic membrane in a synapse, followed by binding to their receptors. Previous studies have shown that the strength of the NT-membrane association is dependent on the lipid composition of the membrane. Negatively charged lipids such as phosphatidylserine, phosphatidylglycerol, and phosphatidic acid have been indicated to promote NT-membrane binding, however these anionic lipids reside almost exclusively in the intracellular leaflet of the post-synaptic membrane instead of the extracellular leaflet facing the synaptic cleft. Meanwhile…

The Role of Hydrophobic Mismatch on Transmembrane Helix Dimerization in Living Cells

Comment on “Finite-size scaling behavior of the tracer surface diffusion coefficient near a second-order phase transition” by F. Nieto et al.

Atomistic Simulations of Functional Au_{144}(SR)_{60} Gold Nanoparticles in Aqueous Environment

Charged monolayer-protected gold nanoparticles (AuNPs) have been studied in aqueous solution by performing atomistic molecular dynamics simulations at physiological temperature (310 K). Particular attention has been paid to electrostatic properties that modulate the formation of a complex comprised of the nanoparticle together with surrounding ions and water. We focus on Au-144 nanoparticles that comprise a nearly spherical Au core (diameter similar to 2 nm), a passivating Au-S interface, and functionalized alkanethiol chains. Cationic and anionic AuNPs have been modeled with amine and carboxyl terminal groups and Cl-/Na+ counterions, respectively. The radial distribution functions show tha…

Memory effects and coverage dependence of surface diffusion in a model adsorption system

We study the coverage dependence of surface diffusion coefficients for a strongly interacting adsorption system O/W(110) via Monte Carlo simulations of a lattice-gas model. In particular, we consider the nature and emergence of memory effects as contained in the corresponding correlation factors in tracer and collective diffusion. We show that memory effects can be very pronounced deep inside the ordered phases and in regions close to first and second order phase transition boundaries. Particular attention is paid to the details of the time dependence of memory effects. The memory effect in tracer diffusion is found to decay following a power law after an initial transient period. This beha…

Comment on “Surface diffusion near the points corresponding to continuous phase transitions” [J. Chem. Phys. 109, 3197 (1998)]

It is well known that unlike static equilibrium properties, kinetic quantities in Monte Carlo simulations are very sensitive to the details of the algorithm used for the microscopic transition rates. This is particularly true near the critical region where fluctuations are pronounced. We demonstrate that when diffusion of oxygen adatoms near the order–disorder transition of a lattice-gas model of the O/W(110) model system is studied, the transition rates must be chosen carefully. In particular, we show that the choice by Uebing and Zhdanov [J. Chem. Phys. 109, 3197 (1998)] is inappropriate for the study of critical effects in diffusion.

Atomistic Simulations of Functional Gold Nanoparticles Au144(Sr)60 Interacting with Membranes

Gold nanoparticles (AuNps) are used in nanomedicine in, e.g., drug delivery and bio-imaging. However, it is regrettable that the understanding of nanoparticle properties in cellular surroundings is incompletely understood. Here, we have complemented our previous studies [1] by performing extensive atomistic molecular dynamics simulations of lipid membranes interacting with charged gold nanoparticles. We have elucidated the action of these nanoparticles on membranes characterized by lipid compositional asymmetry in the two leaflets, thereby unraveling the interactions of AuNPs with both the extracellular and the cytosolic sides of plasma membranes of eukaryotic cells. We have found that ther…

A dynamical mean field theory for the study of surface diffusion constants

We present a combined analytical and numerical approach based on the Mori projection operator formalism and Monte Carlo simulations to study surface diffusion within the lattice-gas model. In the present theory, the average jump rate and the susceptibility factor appearing are evaluated through Monte Carlo simulations, while the memory functions are approximated by the known results for a Langmuir gas model. This leads to a dynamical mean field theory (DMF) for collective diffusion, while approximate correlation effects beyond DMF are included for tracer diffusion. We apply our formalism to three very different strongly interacting systems and compare the results of the new approach with th…

Topology and structure of Au144(SRNH3+)60 from "Atomistic Simulations of Functional Au144(SR)60 Gold Nanoparticles in Aqueous Environment"

Positively charged monolayer-protected gold nanoparticles (AuNPs) structure and topology files for GROMACS used in DOI: 10.1021/jp301094m. The final structure of the simulation reported in DOI: 10.1021/jp301094m for the neutral case is provided. The gold nanoparticle contain a core of 144 Au atoms and 60 functionalized alkanethiol side groups (undecanyl chain, R = C11H22), each possessing a positively charged amonium terminal group. When using this structure do not forget to cite DOI: 10.1021/jp301094m. NOTE1: Different versions for the topology files are provided of both AuNPs. All versions were used for the publication. The changes only affect the core surface and therefore had no influ…

Topology and structure of Au144(SRCOO-)60 from "Atomistic Simulations of Functional Au144(SR)60 Gold Nanoparticles in Aqueous Environment"

Negatively charged monolayer-protected gold nanoparticles (AuNPs) structure and topology files for GROMACS used in DOI: 10.1021/jp301094m. The final structure of the simulation reported in DOI: 10.1021/jp301094m for the neutral case is provided. The gold nanoparticle contain a core of 144 Au atoms and 60 functionalized alkanethiol side groups (undecanyl chain, R = C11H22), each possessing a negatively charged carboxylic terminal group. When using this structure do not forget to cite DOI: 10.1021/jp301094m. NOTE1: Different versions for the topology files are provided of both AuNPs. All versions were used for the publication. The changes only affect the core surface and therefore had no in…