Meenakshi Dutt

Modeling the Self-Assembly of Lipids and Nanotubes in Solution: Forming Vesicles and Bicelles with Transmembrane Nanotube Channels

Via dissipative particle dynamics (DPD), we simulate the self-assembly of end-functionalized, amphiphilic nanotubes and lipids in a hydrophilic solvent. Each nanotube encompasses a hydrophobic stalk and two hydrophilic ends, which are functionalized with end-tethered chains. With a relatively low number of the nanotubes in solution, the components self-assemble into stable lipid-nanotube vesicles. As the number of nanotubes is increased, the system exhibits a vesicle-to-bicelle transition, resulting in stable hybrid bicelle. Moreover, our results reveal that the nanotubes cluster into distinct tripod-like structures within the vesicles and aggregate into a ring-like assembly within the bicelles. For both the vesicles and bicelles, the nanotubes assume trans-membrane orientations, with the tethered hairs extending into the surrounding solution or the encapsulated fluid. Thus, the hairs provide a means of regulating the transport of species through the self-assembled structures. Our findings provide guidelines for creating nanotube clusters with distinctive morphologies that might be difficult to achieve through more conventional means. The results also yield design rules for creating synthetic cell-like objects or microreactors that can exhibit biomimetic functionality.

An implementation of granular dynamics for simulating frictional elastic particles based on the DL_POLY code

We have modified Daresbury Laboratorys replicated data strategy (RDS) parallel molecular dynamics (MD) package DL_POLY (version 2.13) to study the granular dynamics of frictional elastic particles. DL_POLY [Smith and Forester, The DL_POLY_2 User Manual v2.13, 2001; Forester and Smith, The DL_POLY_2 Reference Manual v2.13, 2001] is a MD package originally developed to study liquid state and macromolecular systems by accounting for various molecular interaction forces. The particles of interest in this study are macroscopic grains in pharmaceutical powders, with sizes ranging from tens to hundreds of microns. We have therefore substituted the molecular interaction forces with contact forces (including linear-dashpot, HKK interaction forces and Coulombic friction) while taking advantage of the RDS scheme. In effect, we have created a parallel Discrete Element Simulation (DES) code. In this paper, we describe the modifications made to the original DL_POLY code and the results from the validation tests of the granular dynamics simulations for systems of monodisperse spherical particles settling under gravity. The code can also be utilized to study particle packings generated via uniaxial compaction and, in some cases, simultaneous application of shear, at constant strain.

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.

Bioinspired Vesicles Encompassing Two-Tail Phospholipids: Self-Assembly and Phase Segregation via Implicit Solvent Coarse-Grained Molecular Dynamics

Via implicit solvent molecular dynamics simulations, we demonstrate the self-assembly of stable single and binary vesicles composed of two-tail phospholipid molecules. The amphiphilic lipid molecules are composed of a hydrophilic headgroup and two hydrophobic tails and are represented by a reduced coarse-grained model which effectively captures the key chemical and geometric attributes of phospholipid molecules. We report our measurements of the bilayer thickness to be consistent with experimental values reported in the literature. We have probed the role of temperature on the physical properties of single component lipid vesicles and found our results to concur with experimental results. Our investigations on the phase segregation in binary vesicles demonstrate that the degree of distinction between the tail groups of the lipid species can be used to tune their phase segregation in the vesicle bilayer. Finally, our measurements of the scaling exponents for macroscopically phase-segregated systems have been found to be in good agreement with theoretical and simulation studies. Our results can be used for the design of responsive biomaterials for applications in drug delivery, sensing, and imaging.

Self-Assembly and Critical Aggregation Concentration Measurements of ABA Triblock Copolymers with Varying B Block Types: Model Development, Prediction, and Validation

The dissipative particle dynamics (DPD) simulation technique is a coarse-grained (CG) molecular dynamics-based approach that can effectively capture the hydrodynamics of complex systems while retaining essential information about the structural properties of the molecular species. An advantageous feature of DPD is that it utilizes soft repulsive interactions between the beads, which are CG representation of groups of atoms or molecules. In this study, we used the DPD simulation technique to study the aggregation characteristics of ABA triblock copolymers in aqueous medium. Pluronic polymers (PEG-PPO-PEG) were modeled as two segments of hydrophilic beads and one segment of hydrophobic beads. Tyrosine-derived PEG5K-b-oligo(desaminotyrosyl tyrosine octyl ester-suberate)-b-PEG5K (PEG5K-oligo(DTO-SA)-PEG5K) block copolymers possess alternate rigid and flexible components along the hydrophobic oligo(DTO-SA) chain, and were modeled as two segments of hydrophilic beads and one segment of hydrophobic, alternate soft and hard beads. The formation, structure, and morphology of the initial aggregation of the polymer molecules in aqueous medium were investigated by following the aggregation dynamics. The dimensions of the aggregates predicted by the computational approach were in good agreement with corresponding results from experiments, for the Pluronic and PEG5K-oligo(DTO-SA)-PEG5K block copolymers. In addition, DPD simulations were utilized to determine the critical aggregation concentration (CAC), which was compared with corresponding results from an experimental approach. For Pluronic polymers F68, F88, F108, and F127, the computational results agreed well with experimental measurements of the CAC measurements. For PEG5K-b-oligo(DTO-SA)-b-PEG5K block polymers, the complexity in polymer structure made it difficult to directly determine their CAC values via the CG scheme. Therefore, we determined CAC values of a series of triblock copolymers with 3-8 DTO-SA units using DPD simulations, and used these results to predict the CAC values of triblock copolymers with higher molecular weights by extrapolation. In parallel, a PEG5K-b-oligo(DTO-SA)-b-PEG5K block copolymer was synthesized, and the CAC value was determined experimentally using the pyrene method. The experimental CAC value agreed well with the CAC value predicted by simulation. These results validate our CG models, and demonstrate an avenue to simulate and predict aggregation characteristics of ABA amphiphilic triblock copolymers with complex structures.

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.

Quantitative analysis of packed and compacted granular systems by x-ray microtomography

The packing and compaction of powders are general processes in pharmaceutical, food, ceramic and powder metallurgy industries. Understanding how particles pack in a confined space and how powders behave during compaction is crucial for producing high quality products. This paper outlines a new technique, based on modern desktop X-ray tomography and image processing, to quantitatively investigate the packing of particles in the process of powder compaction and provide great insights on how powder densify during powder compaction, which relate in terms of materials properties and processing conditions to tablet manufacture by compaction. A variety of powder systems were considered, which include glass, sugar, NaCl, with a typical particle size of 200-300 μm and binary mixtures of NaCl-Glass Spheres. The results are new and have been validated by SEM observation and numerical simulations using discrete element methods (DEM). The research demonstrates that XMT technique has the potential in further investigating of pharmaceutical processing and even verifying other physical models on complex packing.

Energy dissipation and clustering for a cooling granular material on a substrate

Abstract We experimentally study the dynamics of a cooling two-dimensional granular system of steel spheres moving radially inward on an aluminum substrate. We find that the cooling process in this system differs significantly from model calculations that include realistic restitutional losses and rolling (hence, weak) friction. A likely explanation for the experimental observations is the fact that particles typically slide on the substrate for some time after each collision, losing energy rapidly. Using results from an MD simulation as a reference point, we consider detailed experimental results for the cooling of systems of spheres on a substrate as a function of the system size, N . For systems with more than N =300 particles, we find that final spatial configurations consist primarily of dense central clusters, and that the velocity distributions, which have an exponential character, are only weakly dependent on system size. Thus, there is a critical system size above which a majority of particles come to rest in a densely packed lattice. We also find evidence of a spatial ordering size scale in the cooled state that is much smaller than the system size. Velocity distributions in the cooling system are nearly Maxwell–Boltzmann (MB)-like at early times, but show significant differences from a MB distribution after particles have undergone a moderate number of collisions.

Implicit solvent coarse‐grained model of polyamidoamine dendrimers: Role of generation and pH

Highly branched polymers such as polyamidoamine (PAMAM) dendrimers are promising macromolecules in the realm of nanobiotechnology due to their high surface coverage of tunable functional groups. Modeling efforts of PAMAM can provide structural and morphological properties, but the inclusion of solvents and the exponential growth of atoms with generations make atomistic simulations computationally expensive. We apply an implicit solvent coarse‐grained model, called the Dry Martini force field, to PAMAM dendrimers. The reduced number of particles and the absence of a solvent allow the capture of longer spatiotemporal scales. This study characterizes PAMAM dendrimers of generations one through seven in acidic, neutral, and basic pH environments. Comparison with existing literature, both experimental and theoretical, is done using measurements of the radius of gyration, moment of inertia, radial distributions, and scaling exponents. Additionally, ion coordination distributions are studied to provide insight into the effects of interior and exterior protonation on counter ions. This model serves as a starting point for future designs of larger functionalized dendrimers.

Applications of DL_POLY to modelling of mesoscopic particulate systems

The molecular dynamics package DL_POLY has at its heart a number of versatile and efficient dynamics algorithms that can readily be adapted to extend the application of this code well beyond the time and length scales typically associated with atomistic simulations. In order to achieve this, it is necessary to substitute the appropriate interparticle potentials and forces in place of the default functional forms in DL_POLY, which are mainly suitable for molecular systems. To facilitate this, it may be required to incorporate additional factors, into the simulation, such as velocity-dependent dissipation effects (friction), rotational degrees of freedom and non-spherosymmetric forces. In this paper, we will discuss some of the practical details of implementing these changes to DL_POLY (version 2) together with applications of discrete particle dynamics methods, such as dissipative particle dynamics (DPD) and granular dynamics (GD) (also known as the discrete or distinct element method, DEM) to particle packing in composite systems and pharmaceutical powders. We also consider how well the approach of simulating particles of arbitrary shape using rigid assemblies of fused soft spheres (each individually interacting via pairwise continuous potentials) compares to true hard-body simulations of polygonal particles.