Determination of mean and Gaussian curvatures of highly curved asymmetric lipid bilayers: the case study of the influence of cholesterol on the membrane shape.

Although molecular dynamics simulations of highly curved lipid bilayers have become increasingly popular in recent years, there is no simple and general method of computing the shape and curvature of the bilayer, which is bent arbitrarily in three dimensions. In this work we propose a method, which allows computing local normal, mean and Gaussian curvatures at any point of an arbitrarily curved lipid membrane using molecular dynamics trajectories. The method is based on the analysis of local membrane patches and is applicable to the membranes of any shape and topology - bilayers, vesicles, micelles, bicelles, etc. The method is applied to a highly curved asymmetric DOPC/DOPS lipid bilayer simulated by means of extended coarse-grained molecular dynamics simulations. It is shown that addition of cholesterol makes the membrane more topologically heterogeneous by increasing the content of highly curved regions with either saddle-like or sphere-like topology. The topology of the DOPS lipid domains is more sensitive to the addition of cholesterol than DOPC domains.

Theoretical study of amino derivatives and anticancer platinum drug grafted on various carbon nanostructures.

Density functional theory calculations with van der Waals approximation have been conducted to analyze the functionalization of various carbon-based nanostructures (fullerene, metallic, and semi-conducting nanotubes) with amino derivative groups. The results obtained with azomethine, show the formation of a five membered ring on fullerenes, and on nanotubes consistent with experimental observations. The attachment of an azomethine plus subsequent drug like a Pt(IV) complex does not perturb the cycloaddition process. Moreover, all theoretical results show that the length of different amino derivatives with subsequent Pt(IV) complex does not affect the complexed therapeutic agent when it is attached onto these carbon-based nanostructures.

Cholesterol induces uneven curvature of asymmetric lipid bilayers.

A remarkable flexibility is observed in biological membranes, which allows them to form the structures of different curvatures. We addressed the question of intrinsic ability of phospholipid membranes to form highly curved structures and the role of cholesterol in this process. The distribution of cholesterol in the highly curved asymmetric DOPC/DOPS lipid bilayer was investigated by the coarse-grained molecular dynamics simulations in the membrane patches with large aspect ratio. It is shown that cholesterol induces uneven membrane curvature promoting the formation of extended flattened regions of the membrane interleaved by sharp bends. It is shown that the affinity of cholesterol to anionic DOPS or neutral DOPC lipids is curvature dependent. The cholesterol prefers DOPS to DOPC in either planar or highly curved parts of the membrane. In contrast, in the narrow interval of moderate membrane curvatures this preference is inverted. Our data suggest that there is a complex self-consistent interplay between the membrane curvature and cholesterol distribution in the asymmetric lipid bilayers. The suggested new function of cholesterol may have a biological relevance.

Synthesis, evaluation and molecular modelling of piceatannol analogues as arginase inhibitors.

Arginase is involved in a wide range of pathologies including cardiovascular diseases and infectious diseases whilst it is also a promising target to improve cancer immunotherapy. To date, only a limited number of inhibitors of arginase have been reported. Natural polyphenols, among them piceatannol, are moderate inhibitors of arginase. Herein, we report our efforts to investigate catechol binding by quantum chemistry and generate analogues of piceatannol. In this work, we synthesized a novel series of amino-polyphenols which were then evaluated as arginase inhibitors. Their structure-activity relationships were elucidated by deep quantum chemistry modelling. 4-((3,4-Dihydroxybenzyl)amino)benzene-1,2-diol 3t displays a mixed inhibition activity on bovine and human arginase I with IC50 (K i) values of 76 (82) µM and 89 µM, respectively.

Determination of the shape and curvature of nonplanar lipid bilayers that are bent in a single plane in molecular dynamics simulations.

The curvature of biological membranes is known to be an important influence on important phenomena such as membrane fusion, endocytosis, and the functioning of integral membrane proteins. There is a growing demand for analytical tools that are able accommodate molecular dynamics trajectories of significantly curved lipid bilayers. In this work, an algorithm for determining the shape and curvature of a nonplanar lipid bilayer in molecular dynamics simulations is proposed. The algorithm calculates the coordinates of the midline and the curvature of the bilayer as well as the local normal to it at any point on the membrane, which is bent arbitrarily in a single plane and is topologically equivalent to an infinite bilayer. The algorithm is implemented as a C++ program and tested by exploring the molecular dynamic trajectories of a highly curved meander-like asymmetric lipid bilayer. The algorithm is general enough to allow it to be easily applied to other geometries of nonplanar membrane systems.

Insertion kinetics of small nucleotides through single walled carbon nanotube.

We report molecular dynamic simulations showing that a DNA molecule constituted by five unique bases can be spontaneously inserted into single walled carbon nanotube (SWCNT) in normal conditions (P, T and water environment) depending on the tube radius value. The van der Waals and electrostatic interactions play a central role for the rapid insertion process. Our study shows also that the Guanine molecule inserts the fastest compared to thymine, adenine and cytosine bases, respectively. The differences of insertion time could be exploited for applications concerning for example DNA sequencing.

Nondestructive room-temperature adsorption of 2,4,6-tri(2'-thienyl)-1,3,5-triazine on a Si-B interface: high-resolution STM imaging and molecular modeling.

Organic nanostructures on semiconductors are currently investigated but the surfaces are known to interact strongly with molecules. To reduce the molecule-surface interaction, we used the Si(111)-B square root 3 x square root 3R30 degrees . Deposition of isolated 2,4,6-tri(2'-thienyl)-1,3,5-triazine, was achieved at room temperature without modification of their pi skeleton. This fascinating arrangement, observed by STM, has been validated by full density functional theory computations onto the entire system. The theoretical results give a clear explanation for the specific adsorption sites of molecules on the substrate.

Characterization of single wall carbon nanotubes by means of rare gas adsorption.

Based on the formalisms of Langmuir and Fowler, theoretical adsorption isotherms are calculated for different bundle geometries of single wall carbon nanotubes in a triangular lattice. The authors show the dependence of the adsorption properties on the nanotube diameter and on the specific morphology of the bundles they constitute. The authors demonstrate how isotherm curve analysis can help to experimentally determine what kinds of tubes form a given bundle and the ratio of open to closed tubes in a sample having undergone a complete or incomplete opening protocol. In spite of the model's simplicity, quite satisfactory agreement is observed between experiments and the authors' calculations.

Role of water molecules in the KcsA protein channel by molecular dynamics calculations.

Molecular dynamics simulations supported by electrostatic calculations have been conducted on the KcsA channel to determine the role of water molecules in the pore. Starting from the X-ray structure of the KcsA channel in its closed state at 2.0 angstroms resolution, the opening of the pore towards a conformation built on the basis of EPR results is studied. We show that water molecules act as a structural element for the K+ ions inside the filter and the hydrophobic cavity of the channel. In the filter, water tends to enhance the depth of the wells occupied by the K+ ions, while in the cavity there is a strong correlation between the water molecules and the cavity ion. As a consequence, the protein remains very stable in the presence of three K+ ions in the selectivity filter and one in the cavity. The analysis of the dynamics of water molecules in the cavity reveals preferred orientations of the dipoles along the pore axis, and a correlated behavior between this dipole orientation and the displacement of the K+ ion during the gating process.

[Failure conditions of glass filament yarns: a contribution to the valuation of carcinogenic potentials of fiber fragments]. / Bruchverhalten von Glasfilamentgarnen: Ein Beitrag zur Beurteilung des kanzerogenen Potentials der Faserbruchstücke.

Failure of glass filament yarns results in the formation of many fragments. Through inhalation, these particles can intrude into the human body. If the fragments are sufficiently bioresistant and have a fiber dust geometry, according to the MAK-values (6), i.e. if they are longer than 5 microns and thinner than 3 microns and show an aspect ratio greater than 3, they have a carcinogenic potential. Since the glass filaments show a diameter greater than 3 microns, no fiber dust particles will be formed if transversal fiber failure occurs without crack-branching. In the present study the geometric distribution of fragments after failure of glass filament yarns under combined stress was investigated in order to estimate the carcinogenic potential of the fragments. The knot tension test was shown to be a suitable method for this investigation. A defined fraction of the total amount of fragments were analysed with scanning electron microscopy (SEM) by measuring their length and diameter. To investigate whether the analysed particles are fragments of the glass filament yarns, chemical analysis was performed with energy dispersive X-ray analysis (EDX). Morphologically, two different fragment types were observed: a) Fragments with their entire filament cross-section which were formed by transversal fiber fraction. b) Smaller fragments which were formed through crack-branching. These smaller fragments were observed to adhere on the bigger fragments due to high surface forces. During each knot tension test, 5-60 fragments per filament were formed. However, the fraction of fiber dust particles was very low and showed a maximum of 1.5%. Only in one of the four tested yarn types (high temperature yarn HT 75) the formation of fiber dust particles was observed. The other yarns showed fragments with dimensions close to fiber dust geometry. Therefore, it cannot be excluded that some fragments with fiber dust geometry may have been formed during mechanical testing. Fragment distribution of the studied E-glass yarns was shown to be dependent on the modification method. To date, it cannot be excluded that there are types of glass filament yarns forming a major quantity of fiber dust particles during failure. The fragments of type b such as fiber dust particles were observed to adhere on bigger fragments which are themselves too big to reach the alveoli. In the present study the stability of these agglomerates under various environmental conditions was not investigated. Moreover, fragment agglomerates should not be considered on their own but in connection with the application. The presented tests were carried out with simple yarns and, therefore, represent isolated observations.

Effect of an atomically thin dielectric film on the surface electron dynamics: image-potential states in the Ar/Cu(100) system.

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