Collective dynamics of molecular rotors in periodic mesoporous organosilica: a combined solid-state 2H-NMR and molecular dynamics simulation study.

Molecular rotors offer a platform to realize controlled dynamics and modulate the functions of solids. The motional mechanisms in arrays of rotors have not been explored in depth. Crystal-like porous organosilicas, comprising p-phenylene rotators pivoted onto a siloxane scaffold, were modelled using molecular dynamics (MD) simulations. Long simulations, on a microsecond scale, allowed to follow the reorientation statistics of rotor collections and single out group configurations and frequency distributions as a function of temperature. The motions observed in the MD simulations support a multiple-site model for rotor reorientations. Computed motional frequencies revealed a complex rotatory phenomenon combining an ultra-fast libration motion (oscillation up to 30°) with a slow and fast 180° flip reorientation. Adopting a multiple-site model provides a more accurate simulation of the 2H-NMR spectra and a rationalization of their temperature dependence. In particular, rotators endowed with distinct rates could be explained by the presence of slower rings locked in a T-shaped conformation.

An Integrated Fusion Engine for Early Threat Detection Demonstrated in Public-Space Trials.

Counter terrorism is a huge challenge for public spaces. Therefore, it is essential to support early detection of threats, such as weapons or explosives. An integrated fusion engine was developed for the management of a plurality of sensors to detect threats without disrupting the flow of commuters. The system improves security of soft targets (such as airports, undergrounds and railway stations) by providing security operators with real-time information of the threat combined with image and position data of each person passing the monitored area. This paper describes the results of the fusion engine in a public-space trial in a metro station in Rome. The system consists of 2D-video tracking, person re-identification, 3D-video tracking, and command and control (C&C) formulating two co-existing data pipelines: one for visualization on smart glasses and another for hand-over to another sensor. Over multiple days, 586 commuters participated in the trial. The results of the trial show overall accuracy scores of 97.4% and 97.6% for the visualization and hand-over pipelines, respectively, and each component reached high accuracy values (2D Video = 98.0%, Re-identification = 100.0%, 3D Video = 99.7% and C&C = 99.5%).

Atomistic hybrid particle-field molecular dynamics combined with slip-springs: Restoring entangled dynamics to simulations of polymer melts.

In hybrid particle-field (hPF) simulations (J. Chem. Phys., 2009 130, 214106), the entangled dynamics of polymer melts is lost due to chain crossability. Chains cross, because the field-treatment of the nonbonded interactions makes them effectively soft-core. We introduce a multi-chain slip-spring model (J. Chem. Phys., 2013 138, 104907) into the hPF scheme to mimic the topological constraints of entanglements. The structure of the polymer chains is consistent with that of regular molecular dynamics simulations and is not affected by the introduction of slip-springs. Although slight deviations are seen at short times, dynamical properties such as mean-square displacements and reorientational relaxation times are in good agreement with traditional molecular dynamics simulations and theoretical predictions at long times.

A Molecular Interpretation of the Dynamics of Diffusive Mass Transport of Water within a Glassy Polyetherimide.

The diffusion process of water molecules within a polyetherimide (PEI) glassy matrix has been analyzed by combining the experimental analysis of water sorption kinetics performed by FTIR spectroscopy with theoretical information gathered from Molecular Dynamics simulations and with the expression of water chemical potential provided by a non-equilibrium lattice fluid model able to describe the thermodynamics of glassy polymers. This approach allowed us to construct a convincing description of the diffusion mechanism of water in PEI providing molecular details of the process related to the effects of the cross- and self-hydrogen bonding established in the system on the dynamics of water mass transport.

Genomic analysis reveals association of specific SNPs with athletic performance and susceptibility to injuries in professional soccer players.

The development of specific and individualized training programs is a possible way to improve athletic performance and minimize injuries in professional athletes. The information regarding the sport's physical demands and the athletes' physical profile have been, so far, considered as exhaustive for the design of effective training programs. However, it is currently emerging that the genetic profile has to be also taken into consideration. By merging medical and genetic data, it is thus possible to identify the athlete's specific attitude to respond to training, diet, and physical stress. In this context, we performed a study in which 30 professional soccer players, subjected to standard sport medical evaluation and practices, were also screened for genetic polymorphism in five key genes (ACTN3, COL5A1, MCT1, VEGF, and HFE). This genetic analysis represents the central point of a multidisciplinary method that can be adopted by elite soccer teams to obtain an improvement in athletic performance and a concomitant reduction of injuries by tailoring training and nutritional programs. The genetic fingerprinting of single athletes led to the identification of two performance-enhancing polymorphisms (ACTN3 18705C>T, VEGF-634C>G) significantly enriched. Moreover, we derived a genetic model based on the gene set analyzed, which was tentatively used to reduce athletes' predisposition to injuries, by dictating a personalized nutrition and training program. The potential usefulness of this approach is concordant with data showing that this team has been classified as the healthiest and least injured team in Europe while covering the highest distance/match with the highest number of high-intensity actions/match.

Hybrid particle-field molecular dynamics under constant pressure.

Hybrid particle-field methods are computationally efficient approaches for modeling soft matter systems. So far, applications of these methodologies have been limited to constant volume conditions. Here, we reformulate particle-field interactions to represent systems coupled to constant external pressure. First, we show that the commonly used particle-field energy functional can be modified to model and parameterize the isotropic contributions to the pressure tensor without interfering with the microscopic forces on the particles. Second, we employ a square gradient particle-field interaction term to model non-isotropic contributions to the pressure tensor, such as in surface tension phenomena. This formulation is implemented within the hybrid particle-field molecular dynamics approach and is tested on a series of model systems. Simulations of a homogeneous water box demonstrate that it is possible to parameterize the equation of state to reproduce any target density for a given external pressure. Moreover, the same parameterization is transferable to systems of similar coarse-grained mapping resolution. Finally, we evaluate the feasibility of the proposed approach on coarse-grained models of phospholipids, finding that the term between water and the lipid hydrocarbon tails is alone sufficient to reproduce the experimental area per lipid in constant-pressure simulations and to produce a qualitatively correct lateral pressure profile.

Biomembrane solubilization mechanism by Triton X-100: a computational study of the three stage model.

The solubilization mechanism of lipid membranes in the presence of Triton X-100 (TX-100) is investigated at molecular resolution using molecular dynamics (MD) simulations. Thanks to the large time and length scales accessible by the hybrid particle-field formulation of the models employed here, the complex process of membrane solubilization has been studied, with the goal of verifying the three stage model reported in the literature. DPPC lipid bilayers and vesicles have been studied at different concentrations of the TX-100 detergent employing coarse grained (CG) models. Systems up to ∼600.000 beads, corresponding to more than 2 millions heavy atoms, have been simulated. Moreover, in order to clarify several experimental pieces of evidence, both slow and fast detergent partition scenarios have been investigated. Flat and curved (vesicles) lipid bilayer surfaces, interacting with TX-100, have been considered to study the curvature effects on the detergent partition rate in the membrane. Shape and conformational changes of mixed DPPC/TX-100 vesicles, as a function of TX-100 content, have also been studied. In particular, high curvature surfaces, corresponding to a higher local TX-100 content, promote a membrane rupture. In flat lipid surfaces, on the time scale simulated the detergent partition is almost absent, following a different pathway of the solubilization membrane mechanism.

Micellar drug nanocarriers and biomembranes: how do they interact?

Pluronic based formulations are among the most successful nanomedicines and block-copolymer micelles including drugs that are undergoing phase I/II studies as anticancer agents. Using coarse-grained models, molecular dynamics simulations of large-scale systems, modeling Pluronic micelles interacting with DPPC lipid bilayers, on the µs timescale have been performed. Simulations show, in agreement with experiments, the release of Pluronic chains from the micelle to the bilayer. This release changes the size of the micelle. Moreover, the presence of drug molecules inside the core of the micelle has a strong influence on this process. The picture emerging from the simulations is that the micelle stability is a result of an interplay of drug-micelle core and block-copolymer-bilayer interactions. The equilibrium size of the drug vector shows a strong dependency on the hydrophobicity of the drug molecules embedded in the core of the micelle. In particular, the radius of the micelle shows an abrupt increase in a very narrow range of drug molecule hydrophobicity.

Flip-flop dynamics in smectic liquid-crystal organic semiconductors revealed by molecular dynamics simulations.

Asymmetric liquid-crystal (LC) organic semiconductors, such as 2-decyl-7-(p-tolyl)-[1]benzothieno[3,2-b][1]benzothiophene (pTol-BTBT-C10), exhibit high mobilities exceeding 10 cm2 V-1 s-1. The LC phases play important roles in thermal stability and self-assembly ordering during film deposition and annealing. In this study, we show molecular dynamics simulations of pTol-BTBT-C10 and reveal a unique mechanism of the molecular flip-flop motion at the smectic E/smectic B phase transition.

A hybrid particle-field molecular dynamics approach: a route toward efficient coarse-grained models for biomembranes.

This paper gives an overview of the coarse-grained models of phospholipids recently developed by the authors in the frame of a hybrid particle-field molecular dynamics technique. This technique employs a special class of coarse-grained models that are gaining popularity because they allow simulations of large scale systems and, at the same time, they provide sufficiently detailed chemistry for the mapping scheme adopted. The comparison of the computational costs of our approach with standard molecular dynamics simulations is a function of the system size and the number of processors employed in the parallel calculations. Due to the low amount of data exchange, the larger the number of processors, the better are the performances of the hybrid particle-field models. This feature makes these models very promising ones in the exploration of several problems in biophysics.

Fully Atomistic Molecular Dynamics Simulation of a TIPS-Pentacene:Polystyrene Mixed Film Obtained via the Solution Process.

Organic thin-film transistors using small-molecule semiconductor materials such as 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS-P) have been recently studied for the production of flexible and printed electronic devices. Blending a semiconductor with an insulating polymer, such as polystyrene, is known to improve the device performance; however, its molecular-level structure remains unknown. In this study, we performed molecular dynamics (MD) simulations on a mixed system of TIPS-P and atactic polystyrene (aPS) with fully atomistic models to understand the structure of the mixed thin film at the molecular level and the influence on the device properties. To reproduce the deposition from the solution, we gradually reduced the number of toluene molecules in the simulation. The dynamic characteristics of the system, mean squared displacement, diffusion coefficient, density profile, and P2 order parameter were analyzed. Some of the simulated systems reached the equilibrium state. In these systems, the simulated structures suggested the presence of more TIPS-P molecules on the surface than inside the bulk, even at the low molecular weight of aPS, where phase separation was not observed experimentally. The results of the fully atomistic MD simulations are also a basis for the coarse-grained model to increase the speed of the MD simulation.

Exploring the Molecular Dynamics of a Lipid-A Vesicle at the Atom Level: Morphology and Permeation Mechanism.

Lipid-A was previously shown to spontaneously aggregate into a vesicle via the hybrid particle field approach. We assess the validity of the proposed vesiculation mechanism by simulating the resulting lipid-A vesicle at the atom level. The spatial confinement imposed by the vesicle geometry on the conformation and packing of lipid-A induces significant heterogeneity of physical properties in the inner and outer leaflets. It also induces tighter molecular packing and lower acyl chain order compared to the lamellar arrangement. Around 5% of water molecules passively permeates the vesicle membrane inward and outward. The permeation is facilitated by interactions with water molecules that are transported across the membrane by a network of electrostatic interactions with the hydrogen bond donors/acceptors in the N-acetylglucosamine ring and upper region of the acyl chains of lipid-A. The permeation process takes place at low rates but still at higher frequencies than observed for the lamellar arrangement of lipid-A. These findings not only substantiate the proposed lipid-A vesiculation mechanism but also reveal the complex structural dynamics of an important nonlamellar arrangement of lipid-A.

Bacterial lipids drive compartmentalization on the nanoscale.

The design of cellular functions in synthetic systems, inspired by the internal partitioning of living cells, is a constantly growing research field that is paving the way to a large number of new remarkable applications. Several hierarchies of internal compartments like polymersomes, liposomes, and membranes are used to control the transport, release, and chemistry of encapsulated species. However, the experimental characterization and the comprehension of glycolipid mesostructures are far from being fully addressed. Lipid A is indeed a glycolipid and the endotoxic part of Gram-negative bacterial lipopolysaccharide; it is the moiety that is recognized by the eukaryotic receptors giving rise to the modulation of innate immunity. Herein we propose, for the first time, a combined approach based on hybrid Particle-Field (hPF) Molecular Dynamics (MD) simulations and Small Angle X-Ray Scattering (SAXS) experiments to gain a molecular picture of the complex supramolecular structures of lipopolysaccharide (LPS) and lipid A at low hydration levels. The mutual support of data from simulations and experiments allowed the unprecedented discovery of the presence of a nano-compartmentalized phase composed of liposomes of variable size and shape which can be used in synthetic biological applications.

Hybrid particle-field molecular dynamics simulations: parallelization and benchmarks.

The parallel implementation of a recently developed hybrid scheme for molecular dynamics (MD) simulations (Milano and Kawakatsu, J Chem Phys 2009, 130, 214106) where self-consistent field theory (SCF) and particle models are combined is described. Because of the peculiar formulation of the hybrid method, considering single particles interacting with density fields, the most computationally expensive part of the hybrid particle-field MD simulation can be efficiently parallelized using a straightforward particle decomposition algorithm. Benchmarks of simulations, including comparisons of serial MD and MD-SCF program profiles, serial MD-SCF and parallel MD-SCF program profiles, and parallel benchmarks compared with efficient MD program GROMACS 4.5.4 are tested and reported. The results of benchmarks indicate that the proposed parallelization scheme is very efficient and opens the way to molecular simulations of large scale systems with reasonable computational costs.

A combined experimental and molecular simulation study on stress generation phenomena during the Ziegler-Natta polyethylene catalyst fragmentation process.

The morphology of particles obtained under different pre-polymerization conditions has been connected to the stress generation mechanism at the polymer/catalyst interface. A combination of experimental characterization techniques and atomistic molecular dynamics simulations allowed a systematic investigation of experimental conditions leading to a certain particle morphology, and hence to a final polymer with specific features. Atomistic models of nascent polymer phases in contact with magnesium dichloride surfaces have been developed and validated. Using these detailed models, in the framework of McKenna's hypothesis, the pressure increase due to the polymerization reaction has been calculated under different conditions and is in good agreement with experimental scenarios. This molecular scale knowledge and the proposed investigation strategy would allow the pre-polymerization conditions to be better defined and the properties of the nascent polymer to be tuned, ensuring proper operability along the whole polymer production process.

Aggregation of Lipid A Variants: A Hybrid Particle-Field Model.

Lipid A is one of the three components of bacterial lipopolysaccharides constituting the outer membrane of Gram-negative bacteria, and is recognized to have an important biological role in the inflammatory response of mammalians. Its biological activity is modulated by the number of acyl-chains that are present in the lipid and by the dielectric medium, i.e., the type of counter-ions, through electrostatic interactions. In this paper, we report on a coarse-grained model of chemical variants of Lipid A based on the hybrid particle-field/molecular dynamics approach (hPF-MD). In particular, we investigate the stability of Lipid A bilayers for two different hexa- and tetra-acylated structures. Comparing particle density profiles along bilayer cross-sections, we find good agreement between the hPF-MD model and reference all-atom simulation for both chemical variants of Lipid A. hPF-MD models of constituted bilayers composed by hexa-acylated Lipid A in water are stable within the simulation time. We further validate our model by verifying that the phase behavior of Lipid A/counterion/water mixtures is correctly reproduced. In particular, hPF-MD simulations predict the correct self-assembly of different lamellar and micellar phases from an initially random distribution of Lipid A molecules with counterions in water. Finally, it is possible to observe the spontaneous formation and stability of Lipid A vesicles by fusion of micellar aggregates.

Simulation of self-heating process on the nanoscale: a multiscale approach for molecular models of nanocomposite materials.

A theoretical-computational protocol to model the Joule heating process in nanocomposite materials is presented. The proposed modeling strategy is based on post processing of trajectories obtained from large scale molecular simulations. This protocol, based on molecular models, is the first one to be applied to organic nanocomposites based on carbon nanotubes (CNT). This strategy allows to keep a microscopic explicit picture of the systems, to directly catch the molecular structure underlying the process under study and, at the same time, to include macroscopic boundary conditions fixed in the experiments. As validation and first application of the proposed strategy, a detailed investigation on CNT based organic composites is reported. The effect of CNT morphologies, concentration and working conditions on Joule heating has been modelled and compared with available experiments. Further experiments are performed also in this work to increase the number of comparisons especially in specific voltage ranges where available references from literature were missing. Simulations are in both qualitative and quantitative agreement with several experiments and trends reported in the recent literature, as well as with experiments performed in this work. The proposed approach combined with large scale hybrid particle-field molecular simulations can give insights and opens to way to a rational design of self-heating nanocomposites.

Effect of Trapped Solvent on the Interface between PS-b-PMMA Thin Films and P(S-r-MMA) Brush Layers.

The orientation of block copolymer (BCP) features in thin films can be obtained by spin-coating a BCP solution on a substrate surface functionalized by a polymer brush layer of the appropriate random copolymer (RCP). Although this approach is well established, little work reporting the amount and distribution of residual solvent in the polymer film after the spin-coating process is available. Moreover, no information can be found on the effect of trapped solvent on the interface between the BCP film and RCP brush. In this work, systems consisting of poly(styrene)-b-poly(methyl methacrylate) thin films deposited on poly(styrene-r-methyl methacrylate) brush layers are investigated by combining neutron reflectivity (NR) experiments with simulation techniques. An increase in the amount of trapped solvent is observed by NR as the BCP film thickness increases accompanied by a significant decrease of the interpenetration length between the BCP and RCP, thus suggesting that the interpenetration between grafted chains and block copolymer chains is hampered by the solvent. Hybrid particle-field molecular dynamics simulations of the analyzed system confirm the experimental observations and demonstrate a clear correlation between the interpenetration length and the amount of trapped solvent.

Micellization of Pluronic P123 in Water/Ethanol/Turpentine Oil Mixed Solvents: Hybrid Particle-Field Molecular Dynamic Simulation.

The hybrid particle-field molecular dynamics simulation method (MD-SCF) was applied to study the self-assembly of Pluronic PEO20-PPO70-PEO20 (P123) in water/ethanol/turpentine oil- mixed solvents. In particular, the micellization process of P123 at low concentration (less than 20%) in water/ethanol/turpentine oil-mixed solvents was investigated. The aggregation number, radius of gyration, and radial density profiles were calculated and compared with experimental data to characterize the structures of the micelles self-assembled from P123 in the mixed solvent. This study confirms that the larger-sized micelles are formed in the presence of ethanol, in addition to the turpentine oil-swollen micelles. Furthermore, the spherical micelles and vesicles were both observed in the self-assembly of P123 in the water/ethanol/turpentine oil-mixed solvent. The results of this work aid the understanding of the influence of ethanol and oil on P123 micellization, which will help with the design of effective copolymer-based formulations.

Nanoparticles at Biomimetic Interfaces: Combined Experimental and Simulation Study on Charged Gold Nanoparticles/Lipid Bilayer Interfaces.

The poor understanding of the interaction of nanomaterials with biologically relevant interfaces is recognized as one of the major issues currently limiting the development of nanomedicine. The central purpose of this study is to compare experimental (confocal microscopy, fluorescence correlation spectroscopy, X-ray reflectivity) and computational (molecular dynamics simulations) results to thoroughly describe the interaction of cationic gold nanoparticles (AuNPs) with mixed zwitterionic/anionic lipid membranes. The adhesion of AuNPs to the lipid membrane is investigated on different length scales from a structural and dynamical point of view; with this approach, a series of complex phenomena, spanning from lipid extraction, localized membrane disruption, lateral phase separation, and slaved diffusion, are characterized and interpreted from a molecular level to macroscopic observations.