Abstract The composition of the plasma membrane malignant cells is thought to influence cellular uptake cisplatin and take part in developing resistance this widespread anti-cancer drug. In work we study permeation through model membranes normal cancer using molecular dynamics simulations. A special attention paid lipid asymmetry cholesterol content membranes. loss asymmetry, which common for cells, leads a decrease their permeability by one order magnitude comparison cells. change molar...

The distribution of phospholipids across the inner membrane (IM) Gram-negative bacteria is unknown. We demonstrate that IMs Escherichia coli and Yersinia pseudotuberculosis are asymmetric, with a 75%/25% (cytoplasmic/periplasmic leaflet) phosphatidylethanolamine (PE) in rod-shaped cells an opposite E. filamentous cells. In initially PE-lacking cells, nascent PE appears first periplasmic leaflet. As total content increases from nearly zero to 75%, progressively adopt rod shape cytoplasmic...

Abstract Once introduced in the organism, interaction of nanoparticles with various biomolecules strongly impacts their fate. Here we show that made squalene derivative gemcitabine (SQGem) interact lipoproteins (LPs), indirectly enabling targeting cancer cells high LP receptors expression. In vitro and vivo experiments reveal preeminent affinity squalene-gemcitabine bioconjugates towards particles highest cholesterol content silico simulations further display incorporation into hydrophobic...

In this work we conduct a systematic analysis of the influence curvature on various properties realistic model mammalian plasma membrane with asymmetric lipid content monolayers and concentration cholesterol. order to do developed new technique for simulating membranes global restricted any desirable value while keeping free lateral diffusion lipids without introducing artifacts or perturbing structure. We show that thickness hydrophobic core concave monolayer decreases by approximately 1.3...

Carbon nanotubes have been proposed to be efficient nanovectors able deliver genetic or therapeutic cargo into living cells. However, a direct evidence of the molecular mechanism their translocation across cell membranes is still needed. Here, we report on an extensive computational study short (5 nm length) pristine and functionalized single-walled carbon uptake by phospholipid bilayer models using all-atom dynamics simulations. Our data support hypothesis through membrane. We find that...

Study of the mechanisms understanding how chemically functionalized carbon nanotubes internalize into mammalian cells is important in view their design as new tools for therapeutic and diagnostic applications. The initial contact between nanotube cell membrane allows elucidation types interaction that are occurring contribution from functional groups at surface. Here we offer a combination experimental theoretical evidence phases with model cellular membranes. Both data reveal critical...

In this work the permeability of a model asymmetric plasma membrane, for ions, water and anti-cancer drugs cisplatin gemcitabine is studied by means all-atom molecular dynamics simulations. It shown first time that highly curved membrane increases from one to three orders magnitude upon bending depending on compound sign curvature. Our results suggest curvature could be an important factor drug translocation through membrane.

Polymyxins, critical last-resort antibiotics, impact the distribution of membrane-bound divalent cations in outer membrane Gram-negative bacteria. We employed atomistic molecular dynamics simulations to model effect displacing these ions. Two polymyxin-sensitive and two polymyxin-resistant models Salmonella enterica were investigated. First, we found that removal all calcium ions induces global stress on membranes, leading substantial restructuring. Next, used enhanced sampling methods...

The adsorption of small molecules $({\mathrm{N}}_{2},$ ${\mathrm{O}}_{2},$ CO, ${\mathrm{CO}}_{2},$ ${\mathrm{H}}_{2}\mathrm{O},$ and HF) in model ropes carbon nanotubes has been studied to determine the main parameters (stable sites, potential barriers, $\dots{})$ which define ability select through their different behavior diffusion mechanism. When polarization is taken into account semiempirical potentials, it a significant influence on polar species. Examination maps along shows that...

Most studies of the interactions neat and functionalized fullerenes with cells have focused so far on their ability to cross cell membrane envelopes. Membranes are, however, also host a large number proteins responsible for various cellular functions. Among these, ion channels are prominent components nervous system. Recently, it was shown that may act as blockers or modulators variety K+ channels. Here we use computer simulations investigate propensity such nanocompounds bind Our results...

A hybrid nanoporous membrane made of a solid-state polymeric thin film in which an ion channel is confined realized. The primary and extremely encouraging results obtained by confocal fluorescence spectroscopy diffusion measurement demonstrate respectively that (i) the considered channel, is, Gramicidin-A, can be selectively inside nanopores (ii) ionic permeability enhanced. Atomistic molecular simulations are also reported fruitfully compared to experimental findings.

Abstract The role of the 17 disulfide (SS) bridges in preserving native conformation human serum albumin (HSA) is investigated by performing classical molecular dynamics (MD) simulations on protein structures with intact and, respectively, reduced SS bridges. thermal unfolding predict a clear destabilization secondary structure upon reduction as well significant distortion tertiary that revealed changes contacts fraction. effect compactness was tested calculating Gibbs free energy profiles...

A remarkable flexibility is observed in biological membranes, which allows them to form the structures of different curvatures. We addressed question intrinsic ability phospholipid membranes highly curved and role cholesterol this process. The distribution asymmetric DOPC/DOPS lipid bilayer was investigated by coarse‐grained molecular dynamics simulations membrane patches with large aspect ratio. It shown that induces uneven curvature promoting formation extended flattened regions...

Development of fluorescence methods involves the necessity understanding fluorescent probes behavior in their ground and excited states. In case biological membranes, position dyes lipid bilayer response after excitation are necessary parameters to correctly analyze experiments. present work, we focus on two markers, Laurdan (6-lauroyl-2-(N,N-dimethylamino)naphthalene) its derivative C-Laurdan (6-dodecanoyl-2-[N-methyl-N-(carboxymethyl)amino]naphthalene), recently proposed for raft...

Although molecular dynamics simulations of highly curved lipid bilayers have become increasingly popular in recent years, there is no simple and general method computing the shape curvature bilayer, which bent arbitrarily three dimensions. In this work we propose a method, allows local normal, mean Gaussian curvatures at any point an membrane using trajectories. The based on analysis patches applicable to membranes topology - bilayers, vesicles, micelles, bicelles, etc. applied asymmetric...

We have studied the interaction of three clinically promising squalenoylated drugs (gemcitabine-squalene, adenine-squalene, and doxorubicin-squalene) with low-density lipoproteins (LDL) by means atomistic molecular dynamics simulations. It is shown that all accumulate inside LDL particles. This effect promoted squalene moiety, which acts as an anchor drives hydrophilic into hydrophobic core lipid droplet. Our data suggest particles could be a universal carriers in bloodstream. Interaction...

The effect of an atomically thin Ar layer on the image-potential states Cu(100) surfaces is studied in a joint experimental-theoretical study, allowing detailed analysis interaction between surface electron and insulator layer. A microscopic theoretical description developed based mutually polarizing atoms. Account 3D structure allows one to predict energies lifetimes image excellent agreement with observations. layer, even as monolayer, efficiently insulating state from metal.

Inflammation is a mediator of number chronic pathologies. We synthesized the diethyl (9Z,12Z)-octadeca-9,12-dien-1-ylphosphonate, called NKS3, which decreased lipopolysaccharide (LPS)-induced mRNA upregulation proinflammatory cytokines (IL-1β, IL-6 and TNF-α) not only in primary intraperitoneal lung alveolar macrophages, but also freshly isolated mice slices. The in-silico studies suggested that being CD36 agonist, will bind to GPR120. Co-immunoprecipitation proximity ligation assays...

The structure and orientational ordering of ${\mathrm{N}}_{2}$ molecules adsorbed on the Cu(110) surface is investigated in a combined experimental theoretical study. Using He atom diffraction we find that monolayer forms high-order commensurate phase with an oblique unit cell. Minimum energy calculations based realistic potentials show cell contains seven arranged novel type pinwheel unexpected for linear smooth surface. Molecular dynamics simulations corroborate this its remarkable thermal...