Mesoscopic Simulation Technique Research Articles

Exploring the Impact of Lipid Domain Size on the Lifetime: A Dissipative Particle Dynamics Study

In this research, we have used the dissipative particle dynamics (DPD), a mesoscopic simulation technique, in order to investigate the dynamics of lipid domains in near critical temperature. Our specific focus has been on exploring the influence of lipid domain size on its lifetime, which mimics the behavior of lipid rafts within cellular membranes. The lipid membranes used in this study were composed of saturated and unsaturated lipids, which have been immersed in water. Through the simulation of these membranes close to their critical temperature, we have successfully generated fluctuating domains that mimic the lipid rafts observed in cellular systems. We have proposed a method to obtain the lifetime of the fluctuating domains by analyzing the sizes of the lipid domains at specific intervals of time. Our investigations have revealed a linear correlation between the initial size of the lipid domain and its lifetime. Our research finding give an insight into the underlying mechanisms that govern lipid rafts and their vital role in various cellular processes.

Multi-scale simulation of deformation and recrystallization of austenitic stainless steels with solidified columnar crystal structures

Columnar grain structures (CCS) often distinct in steel ingots, which have to be refined and homogenized during forging. In this investigation, simulation of deformation and dynamic recrystallization of austenitic stainless steels with CCSs were carried out by macroscopic, mesoscopic (microscopic) and nanoscale simulation techniques. (1) Using molecular dynamics simulation method, the nano-CGSs model with different loading directions was simulated. The results show that the deformation stresses are anisotropic with variation of angles between the loading direction and the columnar crystal growth direction. The higher stresses present at the 0° and 90° angles due to higher dislocation density; However, the lower stresses present at the angles from 30° to 60° due to higher stacking faults and twins. (2) The cellular automata (CA) fractal rules were proposed to simulate nucleation and grain growth of dynamic recrystallization by introducing weighted variables considering Σ3 twin nucleation rate for the twinning-promoted recrystallization. The CA method of nucleation at primary columnar crystal boundaries, secondary dendrites and deformation bands was proposed to simulate the joint nucleation. (3) The coupling simulation of macroscopic thermal parameters by finite element method, solidification of columnar structures and hot deformation dynamic recrystallization by CA was realized.

Role of viscoelasticity on the dynamics and aggregation of chemically active sphere-dimers

The impact of complex media on the dynamics of active swimmers has gained a thriving interest in the research community for their prominent applications in various fields. This paper investigates the effect of viscoelasticity on the dynamics and aggregation of chemically powered sphere-dimers by using a coarse-grained hybrid mesoscopic simulation technique. The sphere-dimers perform active motion by virtue of the concentration gradient around the swimmer’s surface, produced by the chemical reaction at one end of the dimer. We observe that the fluid elasticity enhances translational and rotational motion of a single dimer; however, for a pair of dimers, clustering in a particular alignment is more pronounced. In the case of multiple dimers, the kinetics of cluster formation along with their propulsive nature is presented in detail. The key factors influencing the enhanced motility and the aggregation of dimers are the concentration gradients, hydrodynamic coupling, and the microstructures present in the system.

Can we describe charged nanoparticles with electrolyte theories? Insight from mesoscopic simulation techniques

Electrolyte theories enable to describe the structural and dynamical properties of simple electrolytes in solution, such as sodium chloride in water. Using these theories for aqueous solutions of charged nanoparticles is a straightforward route to extract their charge and size from experimental data. Nevertheless, for such strongly asymmetric electrolytes, the validity of the underlying approximations have never been properly challenged with exact simulation results. In the present work, well established mesoscopic numerical simulations are used to challenge the ability of advanced electrolyte theories to predict the electrical conductivity of suspensions of charged nanoparticles, in the salt-free case. The theories under investigation are based on the Debye-Fuoss-Onsager treatment of electrolyte transport. When the nanoparticles are small enough (about 1 nm large), the theoretical results agree remarkably well with the simulation ones, even in the high concentration regime (volume fraction of nanoparticles larger than 3%). Strikingly, for highly charged nanoparticles, the theory is able to capture the non-monotonic variation of the ratio of the electrical conductivity to its value at infinite dilution (ideal value) as a function of the concentration. However, the tested theories fail to describe the conductivity of suspensions containing larger nanoparticles (e.g. of diameter 4 nm). Finally, only small charged nanoparticles can be considered as ions, as far as electrolyte theories are concerned.

SPICES: a particle-based molecular structure line notation and support library for mesoscopic simulation

Simplified Particle Input ConnEction Specification (SPICES) is a particle-based molecular structure representation derived from straightforward simplifications of the atom-based SMILES line notation. It aims at supporting tedious and error-prone molecular structure definitions for particle-based mesoscopic simulation techniques like Dissipative Particle Dynamics by allowing for an interplay of different molecular encoding levels that range from topological line notations and corresponding particle-graph visualizations to 3D structures with support of their spatial mapping into a simulation box. An open Java library for SPICES structure handling and mesoscopic simulation support in combination with an open Java Graphical User Interface viewer application for visual topological inspection of SPICES definitions are provided.

Mesoscopic Simulation Assistant Design of Immiscible Polyimide/BN Blend Films with Enhanced Thermal Conductivity

The mesoscopic simulation technique was applied to describe the phase separation behavior of polyimide blends and used for design of immiscible polyimide/BN blend films with enhanced thermal conductivity. The simulation equilibrium morphologies of different poly(amic acid) (PAA) blend systems were investigated and compared with optical images of corresponding polyimide blend films obtained by experiment. The immiscible polyimide blend films containing nano-/micro-sized BN with vertical double percolation structure were prepared. The result indicated that the thermal conductivity of polyimide blend film with 25 wt% nano-sized BN reached 1.16 W/(m·K), which was 236% increment compared with that of the homogenous film containing the same BN ratio. The significant enhancement in thermal conductivity was attributed to the good phase separation of polyimide matrix, which made the inorganic fillers selectively localized in one continuous phase with high packing density, consequently, forming the effective thermal conductive pathway.

Mesoscopic model for binary fluids

We propose a model for studying binary fluids based on the mesoscopic molecular simulation technique known as multiparticle collision, where the space and state variables are continuous, and time is discrete. We include a repulsion rule to simulate segregation processes that does not require calculation of the interaction forces between particles, so binary fluids can be described on a mesoscopic scale. The model is conceptually simple and computationally efficient; it maintains Galilean invariance and conserves the mass and energy in the system at the micro- and macro-scale, whereas momentum is conserved globally. For a wide range of temperatures and densities, the model yields results in good agreement with the known properties of binary fluids, such as the density profile, interface width, phase separation, and phase growth. We also apply the model to the study of binary fluids in crowded environments with consistent results.

Numerical Simulations of the Digital Microfluidic Manipulation of Single Microparticles.

Single-cell analysis techniques have been developed as a valuable bioanalytical tool for elucidating cellular heterogeneity at genomic, proteomic, and cellular levels. Cell manipulation is an indispensable process for single-cell analysis. Digital microfluidics (DMF) is an important platform for conducting cell manipulation and single-cell analysis in a high-throughput fashion. However, the manipulation of single cells in DMF has not been quantitatively studied so far. In this article, we investigate the interaction of a single microparticle with a liquid droplet on a flat substrate using numerical simulations. The droplet is driven by capillary force generated from the wettability gradient of the substrate. Considering the Brownian motion of microparticles, we utilize many-body dissipative particle dynamics (MDPD), an off-lattice mesoscopic simulation technique, in this numerical study. The manipulation processes (including pickup, transport, and drop-off) of a single microparticle with a liquid droplet are simulated. Parametric studies are conducted to investigate the effects on the manipulation processes from the droplet size, wettability gradient, wetting properties of the microparticle, and particle-substrate friction coefficients. The numerical results show that the pickup, transport, and drop-off processes can be precisely controlled by these parameters. On the basis of the numerical results, a trap-free delivery of a hydrophobic microparticle to a destination on the substrate is demonstrated in the numerical simulations. The numerical results not only provide a fundamental understanding of interactions among the microparticle, the droplet, and the substrate but also demonstrate a new technique for the trap-free immobilization of single hydrophobic microparticles in the DMF design. Finally, our numerical method also provides a powerful design and optimization tool for the manipulation of microparticles in DMF systems.

Harnessing Nanoscale Confinement to Design Sterically Stable Vesicles of Specific Shapes via Self-Assembly.

We design sterically stable biocompatible vehicles with tunable shapes through the self-assembly of a binary mixture composed of amphiphilic molecular species, such as PEGylated lipids, and phospholipids under volumetric confinement. We use a molecular dynamics-based mesoscopic simulation technique called dissipative particle dynamics to resolve the aggregation dynamics, structure, and morphology of the hybrid aggregate. We examine the effect of confinement on the growth dynamics and shape of the hybrid aggregate, and demonstrate the formation of different morphologies, such as oblate and prolate shaped vesicles and bicelles. We perform these investigations by varying the degree of nanoscale confinement, for different relative concentrations of the species and the length of the functional groups. Results from our investigations can be used for the design and prediction of novel hybrid soft materials for applications requiring the encapsulation of therapeutic agents in micro- or nanofluidic channels.

Mesoscopic simulation of phospholipid membranes, peptides, and proteins with molecular fragment dynamics.

Molecular fragment dynamics (MFD) is a variant of dissipative particle dynamics (DPD), a coarse-grained mesoscopic simulation technique for isothermal complex fuids and soft matter systems with particles that are chosen to be adequate fluid elements. MFD choses its particles to be small molecules which may be connected by harmonic springs to represent larger molecular entities in order to maintain a comparatively accurate representation of covalent bonding and molecular characteristics. For this study the MFD approach is extended to accomplish long-term simulations (up to the microsecond scale) of large molecular ensembles (representing millions of atoms) containing phospholipid membranes, peptides, and proteins. For peptides and proteins a generally applicable fragmentation scheme is introduced in combination with specific backbone forces that keep native spatial shapes with adequate levels of flexibility or rigidity. The new approach is demonstrated by MFD simulations of the formation and characteristics of phospholipid membranes and vesicles, vesicle-membrane fusion, the backbone force dependency of the overall structural flexibility of dumbbell-shaped Calmodulin, the stability of subunit-aggregation of tetrameric hemoglobin, and the collaborative interaction of Kalata B1 cyclotides with a phospholipid membrane. All findings are in reasonable agreement with experimental as well as alternative simulation results. Thus, the extended MFD approach may become a new tool for biomolecular system studies to allow for comparatively fast simulative investigations in combination with a comparatively high chemical granularity.

Taylor dispersion of colloidal particles in narrow channels

We use a mesoscopic particle-based simulation technique to study the classic convection-diffusion problem of Taylor dispersion for colloidal discs in confined flow. When the disc diameter becomes non-negligible compared to the diameter of the pipe, there are important corrections to the original Taylor picture. For example, the colloids can flow more rapidly than the underlying fluid, and their Taylor dispersion coefficient is decreased. For narrow pipes, there are also further hydrodynamic wall effects. The long-time tails in the velocity autocorrelation functions are altered by the Poiseuille flow.

The design of shape-tunable hairy vesicles

Via the use of a mesoscopic simulation technique called dissipative particle dynamics, we design sterically stable biocompatible vehicles through the self-assembly of a binary mixture composed of amphiphilic molecular species, such as PEGylated lipids, and phospholipids. We examine the factors controlling the shape of the hairy vesicle, and report the shape to change with molecular stiffness, and dissimilarity in the hydrocarbon tail groups, along with the relative concentration of the species, and the functional group length. We also draw correspondence with experimental studies on the shape transformations of the hairy vesicles through phase diagrams of the reduced volume, the ratio of the minimum and maximum radii, and the interfacial line tension, as a function of the concentration of the hairy lipids and the hydrocarbon tail molecular chain stiffness. Results from our investigations can be used for the design and prediction of novel hybrid soft materials for applications in the encapsulation and delivery of therapeutic agents.

A molecular fragment cheminformatics roadmap for mesoscopic simulation.

BackgroundMesoscopic simulation studies the structure, dynamics and properties of large molecular ensembles with millions of atoms: Its basic interacting units (beads) are no longer the nuclei and electrons of quantum chemical ab-initio calculations or the atom types of molecular mechanics but molecular fragments, molecules or even larger molecular entities. For its simulation setup and output a mesoscopic simulation kernel software uses abstract matrix (array) representations for bead topology and connectivity. Therefore a pure kernel-based mesoscopic simulation task is a tedious, time-consuming and error-prone venture that limits its practical use and application. A consequent cheminformatics approach tackles these problems and provides solutions for a considerably enhanced accessibility. This study aims at outlining a complete cheminformatics roadmap that frames a mesoscopic Molecular Fragment Dynamics (MFD) simulation kernel to allow its efficient use and practical application.ResultsThe molecular fragment cheminformatics roadmap consists of four consecutive building blocks: An adequate fragment structure representation (1), defined operations on these fragment structures (2), the description of compartments with defined compositions and structural alignments (3), and the graphical setup and analysis of a whole simulation box (4). The basis of the cheminformatics approach (i.e. building block 1) is a SMILES-like line notation (denoted fSMILES) with connected molecular fragments to represent a molecular structure. The fSMILES notation and the following concepts and methods for building blocks 2-4 are outlined with examples and practical usage scenarios. It is shown that the requirements of the roadmap may be partly covered by already existing open-source cheminformatics software.ConclusionsMesoscopic simulation techniques like MFD may be considerably alleviated and broadened for practical use with a consequent cheminformatics layer that successfully tackles its setup subtleties and conceptual usage hurdles. Molecular Fragment Cheminformatics may be regarded as a crucial accelerator to propagate MFD and similar mesoscopic simulation techniques in the molecular sciences.Graphical abstractA molecular fragment cheminformatics roadmap for mesoscopic simulation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13321-014-0045-3) contains supplementary material, which is available to authorized users.

Molecular fragment dynamics study on the water-air interface behavior of non-ionic polyoxyethylene alkyl ether surfactants

Molecular Fragment Dynamics (MFD) is a mesoscopic simulation technique based on Dissipative Particle Dynamics (DPD). Whereas DPD beads in general may not necessarily be identified with chemical compounds at all the MFD variant uses specific molecules or molecular fragments as its basic coarse-grained interacting entities (rather than the fine-grained atom types of Molecular Mechanics). MFD can be used to study formulations of drugs and active agents in oil, water and emulsions. MFD simulations of the nonionic polyoxyethylene alkyl ether surfactants C6E6, C10E6, C12E6 and C16E6 at the water-air interface are performed to study their nanoscale structures and surface properties. The simulations of the self-aggregation of the polyoxyethylene alkyl ether surfactants lead to equilibrium nanoscale structures and computationally determined surface tensions which are in agreement with experimental data for different surfactant concentrations [1]. Figure 1

Computational Design of Multi-component Bio-Inspired Bilayer Membranes

Our investigation is motivated by the need to design bilayer membranes with tunable interfacial and mechanical properties for use in a range of applications, such as targeted drug delivery, sensing and imaging. We draw inspiration from biological cell membranes and focus on their principal constituents. In this paper, we present our results on the role of molecular architecture on the interfacial, structural and dynamical properties of bio-inspired membranes. We focus on four lipid architectures with variations in the head group shape and the hydrocarbon tail length. Each lipid species is composed of a hydrophilic head group and two hydrophobic tails. In addition, we study a model of the Cholesterol molecule to understand the interfacial properties of a bilayer membrane composed of rigid, single-tail molecular species. We demonstrate the properties of the bilayer membranes to be determined by the molecular architecture and rigidity of the constituent species. Finally, we demonstrate the formation of a stable mixed bilayer membrane composed of Cholesterol and one of the phospholipid species. Our approach can be adopted to design multi-component bilayer membranes with tunable interfacial and mechanical properties. We use a Molecular Dynamics-based mesoscopic simulation technique called Dissipative Particle Dynamics that resolves the molecular details of the components through soft-sphere coarse-grained models and reproduces the hydrodynamic behavior of the system over extended time scales.

Computational Design of Multi-component Bio-Inspired Bilayer Membranes

Our investigation is motivated by the need to design bilayer membranes with tunable interfacial and mechanical properties for use in a range of applications, such as targeted drug delivery, sensing and imaging. We draw inspiration from biological cell membranes and focus on their principal constituents. In this paper, we present our results on the role of molecular architecture on the interfacial, structural and dynamical properties of bio-inspired membranes. We focus on four lipid architectures with variations in the head group shape and the hydrocarbon tail length. Each lipid species is composed of a hydrophilic head group and two hydrophobic tails. In addition, we study a model of the Cholesterol molecule to understand the interfacial properties of a bilayer membrane composed of rigid, single-tail molecular species. We demonstrate the properties of the bilayer membranes to be determined by the molecular architecture and rigidity of the constituent species. Finally, we demonstrate the formation of a stable mixed bilayer membrane composed of Cholesterol and one of the phospholipid species. Our approach can be adopted to design multi-component bilayer membranes with tunable interfacial and mechanical properties. We use a Molecular Dynamics-based mesoscopic simulation technique called Dissipative Particle Dynamics that resolves the molecular details of the components through soft-sphere coarse-grained models and reproduces the hydrodynamic behavior of the system over extended time scales.

Molecular fragment dynamics study on the water–air interface behavior of non-ionic polyoxyethylene alkyl ether surfactants

Molecular fragment dynamics (MFD) is a mesoscopic simulation technique based on dissipative particle dynamics (DPD). MFD simulations of the self-aggregation of the polyoxyethylene alkyl ether surfactants C6E6, C10E6, C12E6 and C16E6 at the water–air surface lead to equilibrium nanoscale structures and computationally determined surface tensions which are in agreement with experimental data for different surfactant concentrations. Thus, molecular fragment dynamics is a well-suited predictive technique to study the behavior of new surfactant systems.

Molecular simulations of peptides and proteins with Molecular Fragment Dynamics (MFD)

Molecular Fragment Dynamics (MFD) is a mesoscopic simulation technique based on dissipative particle dynamics. The method has been shown to successfully describe the phase behaviour and interfacial tensions of large chemical systems in good agreement with experimental results [1]. Unlike molecular mechanics a MFD simulation is based on coarse-grained molecular fragments rather than fine-grained atom types. The current MFD fragment definition is based on a SMILES like one-dimensional line notation which is visualized with the Structure Diagram Generator of the Chemistry Development Kit (CDK) [2]. For an extension of the MFD technique to chemical ensembles containing peptides and proteins an appropriate molecular fragment cheminformatics tool for their design is in need. This work provides an editor for the construction of peptides and proteins from molecular fragments. It includes building blocks for all 20 proteinogenic amino acids, their charged species and disulfide bonds. A flexible input of one-letter and three-letter amino acid codes is supported. Additionally, the editor has the capability to set charges of side chains manually or automatically.

Design and Characterization of Nanostructured Biomaterials via the Self-assembly of Lipids

ABSTRACTWe are interested in designing nanostructured biomaterials using nanoscopic building blocks such as functionalized nanotubes and lipid molecules. In our earlier work, we summarized the multiple control parameters which direct the equilibrium morphology of a specific class of nanostructured biomaterials. Individual lipid molecules were composed of a hydrophilic head group and two hydrophobic tails. A bare nanotube encompassed an ABA architecture, with a hydrophobic shaft (B) and two hydrophilic ends (A). We introduced hydrophilic hairs at one end of the tube to enable selective transport through the channel. The dimensions of the nanotube were set to minimize its hydrophobic mismatch with the lipid bilayer. We used a Molecular Dynamics-based mesoscopic simulation technique called Dissipative Particle Dynamics which simultaneously resolves the structure and dynamics of the nanoscopic building blocks and the hybrid aggregate. The amphiphilic lipids and functionalized nanotubes self-assembled into a stable hybrid vesicle or a bicelle in the presence of a hydrophilic solvent. We showed that the morphology of the hybrid structures was directed by factors such as the temperature, the rigidity of the lipid molecules, and the concentration of the nanotubes. Another type of hybrid nanostructured biomaterial could be multi-component lipid bilayers. In this paper, we present approaches to design hybrid nanostructured materials using multiple lipid species with different chemistries and molecular chain stiffness.

Designing Nanostructured Hybrid Inorganic-biological Materials via the Self-assembly

ABSTRACTOur objective is to design nanostructured hybrid inorganic-biological materials using the selfassembly of functionalized nanotubes and lipid molecules. In this presentation, we summarize the multiple control parameters which direct the equilibrium morphology of a specific class of nanostructured biomaterials. Individual lipid molecules are composed of a hydrophilic head group and two hydrophobic tails. A bare nanotube encompasses an ABA architecture, with a hydrophobic shaft (B) and two hydrophilic ends (A). We introduce hydrophilic hairs at one end of the tube to enable selective transport through the channel. The dimensions of the nanotube are set to minimize its hydrophobic mismatch with the lipid bilayer. We use a Molecular Dynamicsbased mesoscopic simulation technique called Dissipative Particle Dynamics which simultaneously resolves the structure and dynamics of the nanoscopic building blocks and the hybrid aggregate. The amphiphilic lipids and functionalized nanotubes self-assemble into a stable hybrid vesicle or a bicelle in the presence of a hydrophilic solvent. We demonstrate that the morphology of the hybrid structures is directed by factors such as the temperature, the molecular rigidity of the lipid molecules, and the concentration of the nanotubes. We present material characterization of the equilibrium morphology of the various hybrid nanostructures. A combination of the material characterization and the morphologies of the hybrid aggregates can be used to predict the structure and properties of other hybrid materials.