Hybrid Time-Dependent Ginzburg-Landau Simulations of Block Copolymer Nanocomposites: Nanoparticle Anisotropy.

Block copolymer melts are perfect candidates to template the position of colloidal nanoparticles in the nanoscale, on top of their well-known suitability for lithography applications. This is due to their ability to self-assemble into periodic ordered structures, in which nanoparticles can segregate depending on the polymer-particle interactions, size and shape. The resulting coassembled structure can be highly ordered as a combination of both the polymeric and colloidal properties. The time-dependent Ginzburg-Landau model for the block copolymer was combined with Brownian dynamics for nanoparticles, resulting in an efficient mesoscopic model to study the complex behaviour of block copolymer nanocomposites. This review covers recent developments of the time-dependent Ginzburg-Landau/Brownian dynamics scheme. This includes efforts to parallelise the numerical scheme and applications of the model. The validity of the model is studied by comparing simulation and experimental results for isotropic nanoparticles. Extensions to simulate nonspherical and inhomogeneous nanoparticles are discussed and simulation results are discussed. The time-dependent Ginzburg-Landau/Brownian dynamics scheme is shown to be a flexible method which can account for the relatively large system sizes required to study block copolymer nanocomposite systems, while being easily extensible to simulate nonspherical nanoparticles.

Nanoparticle anisotropy induces sphere-to-cylinder phase transition in block copolymer melts.

Block copolymer nanocomposites including anisotropic nanoparticles have been previously found to co-assemble into complex structures with nanoparticle alignment. Anisotropic nanoparticles with large aspect ratios are found to modify the morphology of block copolymers at modest concentrations, inducing a sphere-to-cylinder phase transition by breaking the local symmetry in the vicinity of a solid particle. This transition takes place over a wide range of NP lengths comparable with the BCP spacing. Controlling the orientation of uniaxial nanoparticles provides additional control over the global orientation of the block copolymer, as previously reported by experiments.

Large scale three dimensional simulations of hybrid block copolymer/nanoparticle systems.

Block copolymer melts self-assemble in the bulk into a variety of nanostructures, making them perfect candidates to template the position of nanoparticles. The morphological changes of block copolymers are studied in the presence of a considerable filling fraction of colloids. Furthermore, colloids can be found to assemble into ordered hexagonally close-packed structures in a defined number of layers when softly confined within the phase-separated block copolymer. A high concentration of interface-compatible nanoparticles leads to complex long-lived block copolymer morphologies depending on the polymeric composition. Macrophase separation between the colloids and the block copolymer can be induced if colloids are unsolvable within the matrix. This leads to the formation of ellipsoid-shaped polymer-rich domains elongated along the direction perpendicular to the interface between block copolymer domains.

Co-assembly of Janus nanoparticles in block copolymer systems.

Block copolymer are ideal matrices to control the localisation of colloids. Furthermore, anisotropic nanoparticles such as Janus nanoparticles possess an additional orientational degree of freedom that can play a crucial role in the formation of highly ordered materials made of block copolymers. This work presents a mesoscopic simulation method to assert the co-assembly of Janus nanoparticles in a block copolymer mixture, finding numerous instances of aggregation and formation of ordered configurations. Comparison with chemically homogeneous neutral nanoparticles shows that Janus nanoparticles are less prone to induce bridging along lamellar domains, thus being a less destructive way to segregate nanoparticles at interfaces. The combination of asymmetric block copolymer and asymmetric Janus nanoparticles can result in assembly of colloids with an even number of layers within the minority domain.

The effect of amidation on the behaviour of antimicrobial peptides.

Aurein 2.6-COOH and aurein 3.1-COOH were studied along with their naturally occurring C-terminally amidated analogues. Circular dichroism (CD) and molecular dynamic (MD) simulations were used to study the effects of amidation on the interaction of antimicrobial peptides (AMPs) with lipid bilayers. CD measurements and MD analysis suggested that both peptide analogues were predominantly random coil and adopted low levels of α-helical structure in solution (<30%) and in the presence of a lipid bilayer the peptides formed a stable α-helical structure. In general, amidated analogues have a greater propensity than the non-amidated peptides to form a α-helical structure. MD simulations predicted that aurein 2.6-COOH and aurein 3.1-CHOOH destabilised lipid bilayers from 1,2-dimyristoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phosphoserine via angled bilayer penetration. They also showed that aurein 2.6-CONH2 and aurein 3.1-CONH2 formed a helix horizontal to the plane of an asymmetric interface.

The role of C-terminal amidation in the membrane interactions of the anionic antimicrobial peptide, maximin H5.

Maximin H5 is an anionic antimicrobial peptide from amphibians, which carries a C-terminal amide moiety, and was found to be moderately haemolytic (20%). The α-helicity of the peptide was 42% in the presence of lipid mimics of erythrocyte membranes and was found able to penetrate (10.8 mN m(-1)) and lyse these model membranes (64 %). In contrast, the deaminated peptide exhibited lower levels of haemolysis (12%) and α-helicity (16%) along with a reduced ability to penetrate (7.8 m Nm(-1)) and lyse (55%) lipid mimics of erythrocyte membranes. Taken with molecular dynamic simulations and theoretical analysis, these data suggest that native maximin H5 primarily exerts its haemolytic action via the formation of an oblique orientated α-helical structure and tilted membrane insertion. However, the C-terminal deamination of maximin H5 induces a loss of tilted α-helical structure, which abolishes the ability of the peptide's N-terminal and C-terminal regions to H-bond and leads to a loss in haemolytic ability. Taken in combination, these observations strongly suggest that the C-terminal amide moiety carried by maximin H5 is required to stabilise the adoption of membrane interactive tilted structure by the peptide. Consistent with previous reports, these data show that the efficacy of interaction and specificity of maximin H5 for membranes can be attenuated by sequence modification and may assist in the development of variants of the peptide with the potential to serve as anti-infectives.

The cooperative behaviour of antimicrobial peptides in model membranes.

A systematic analysis of the hypothesis of the antimicrobial peptides' (AMPs) cooperative action is performed by means of full atomistic molecular dynamics simulations accompanied by circular dichroism experiments. Several AMPs from the aurein family (2.5,2.6, 3.1), have a similar sequence in the first ten amino acids, are investigated in different environments including aqueous solution, trifluoroethanol (TFE), palmitoyloleoylphosphatidylethanolamine (POPE), and palmitoyloleoylphosphatidylglycerol (POPG) lipid bilayers. It is found that the cooperative effect is stronger in aqueous solution and weaker in TFE. Moreover, in the presence of membranes, the cooperative effect plays an important role in the peptide/lipid bilayer interaction. The action of AMPs is a competition of the hydrophobic interactions between the side chains of the peptides and the hydrophobic region of lipid molecules, as well as the intra peptide interaction. The aureins 2.5-COOH and 2.6-COOH form a hydrophobic aggregate to minimize the interaction between the hydrophobic group and the water. Once that the peptides reach the water/lipid interface the hydrophobic aggregate becomes smaller and the peptides start to penetrate into the membrane. In contrast, aurein 3.1-COOH forms only a transient aggregate which disintegrates once the peptides reached the membrane, and it shows no cooperativity in membrane penetration.

A novel form of bacterial resistance to the action of eukaryotic host defense peptides, the use of a lipid receptor.

Host defense peptides show great potential for development as new antimicrobial agents with novel mechanisms of action. However, a small number of resistance mechanisms to their action are known, and here, we report a novel bacterial resistance mechanism mediated by a lipid receptor. Maximin H5 from Bombina maxima bound anionic and zwitterionic membranes with low affinity (Kd > 225 µM) while showing a strong ability to lyse (>55%) and penetrate (π > 6.0 mN m(-1)) these membranes. However, the peptide bound Escherichia coli and 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) membranes with higher affinity (Kd < 65 µM) and showed a very low ability for bilayer lysis (<8%) and partitioning (π > 1.0 mN m(-1)). Increasing levels of membrane DMPE correlated with enhanced binding by the peptide (R(2) = 0.96) but inversely correlated with its lytic ability (R(2) = 0.98). Taken with molecular dynamic simulations, these results suggest that maximin H5 possesses membranolytic activity, primarily involving bilayer insertion of its strongly hydrophobic N-terminal region. However, this region was predicted to form multiple hydrogen bonds with phosphate and ammonium groups within PE head-groups, which in concert with charge-charge interactions anchor the peptide to the surface of E. coli membranes, inhibiting its membranolytic action.

Aurein 2.3 functionality is supported by oblique orientated α-helical formation.

In this study, an amphibian antimicrobial peptide, aurein 2.3, was predicted to use oblique orientated α-helix formation in its mechanism of membrane destabilisation. Molecular dynamic (MD) simulations and circular dichroism (CD) experimental data suggested that aurein 2.3 exists in solution as unstructured monomers and folds to form predominantly α-helical structures in the presence of a dimyristoylphosphatidylcholine membrane. MD showed that the peptide was highly surface active, which supported monolayer data where the peptide induced surface pressure changes>34 mNm(-1). In the presence of a lipid membrane MD simulations suggested that under hydrophobic mismatch the peptide is seen to insert via oblique orientation with a phenylalanine residue (PHE3) playing a key role in the membrane interaction. There is evidence of snorkelling leucine residues leading to further membrane disruption and supporting the high level of lysis observed using calcein release assays (76%). Simulations performed at higher peptide/lipid ratio show peptide cooperativity is key to increased efficiency leading to pore-formation.

Block copolymer nanocontainers.

Using cell dynamics computer simulation, we perform a systematic study of thin block copolymer films around a nanoparticle. Lamellar-, cylinder-, and sphere-forming block copolymers are investigated with respect to different film thicknesses, particle radii, and boundary conditions at the film interfaces. The obtained structures include standing lamellae and cylinders, "onions", cylinder "knitting balls", "golf ball", layered spherical, "virus"-like and mixed morphologies with T-junctions and U-type defects. The kinetics of the structure formation and difference with planar thin films are discussed. Our simulations suggest that novel porous nanocontainers can be formed by the coating of a sacrificial nanobead by a block copolymer layer with a well-controlled nanostructure. In addition, first scanning force microscopy experiments on a model system reveal surface structures similar to those predicted by our simulations.

Diblock copolymers in a cylindrical pore.

We show that a simple Ginzburg-Landau type theory can predict a tremendous rich "zoo" of diblock copolymer morphologies in cylindrical nanopores. Using the cell dynamics simulation we study in detail lamellar-, cylinder-, and eventually sphere-forming diblock copolymers melts in cylindrical nanopores. A very fast simulation method is proposed to be used as a research precursor for more elaborate computational techniques.

Specific features of defect structure and dynamics in the cylinder phase of block copolymers.

We present a systematic study of defects in thin films of cylinder-forming block copolymers upon long-term thermal or solvent annealing. In particular, we consider in detail the peculiarities of both classical and specific topological defects, and conclude that there is a strong "defect structure-chain mobility" relationship in block copolymers. In the systems studied, representative defect configurations provide connectivity of the minority phase in the form of dislocations with a closed cylinder end or classical disclinations with incorporated alternative, nonbulk structures with planar symmetry. In solvent-annealed films with enhanced chain mobility, the neck defects (bridges between parallel cylinders) were observed. This type of nonsingular defect has not been identified in block copolymer systems before. We argue that topological arguments and 2D defect representation, sufficient for lamellar systems, are not sufficient to determine the stability and mobility of defects in the cylindrical phase. In-situ scanning force microscopy measurements are compared with the simulations based on the dynamic self-consistent mean field theory. The close match between experimental measurements and simulation results suggests that the lateral defect motion is diffusion-driven. In addition, 3D simulations demonstrated that the bottom (wetting) layer is only weakly involved into the structure ordering at the free surface. Finally, the morphological evolution is considered with the focus on the motion and interaction of the representative defect configurations.

Kinetic pathways of gyroid-to-cylinder transitions in diblock copolymers under external fields: cell dynamics simulation.

Using cell dynamics simulation we investigate the cubic gyroid morphology of block copolymer melts under simple shear flow and electric field. The electric field should be stronger than a certain critical value to induce transition to a cylindrical phase. In the case of simple steady shear the gyroid-to-cylinder transition was observed even for a very weak shear. Quantitative analysis of pathways of gyroid-to-cylinder transition is performed by means of Minkowski functionals. We found that the kinetics of the gyroid-to-cylinder transition are different under electric field and shear flow. Moreover, the gyroid structure under different strengths of electric field shows different pathways. Different types of intermediates such as five-, four-fold connections and "winding" cylinders are found for different pathways.

Cubic phases of block copolymers under shear and electric fields by cell dynamics simulation. I. Spherical phase.

Cell dynamics simulation is used to investigate pathways of sphere-to-cylinder transition in block copolymer melt under applied simple shear flow and electric field. Both fields can induce the transition when their strength is above some critical value. At weak fields the spherical phase is preserved, with spheres being deformed into ellipsoids. Weak shear flow is found to improve order in the spherical phase. Observed sliding of layers of spheres under shear is very similar to the experimental finding by Hamley et al. [J. Chem. Phys. 108, 6929 (1998)]. The kinetic pathways are sensitive to the degree of microphase separation in the system and hence affected by temperature. The details of the pathways are described by means of Minkowski functionals.

Defect evolution in block copolymer thin films via temporal phase transitions.

We study the details of the defect dynamics in thin films of a cylinder-forming polystyrene-block-polybutadiene (SB) diblock copolymer melt. The high temporal resolution of in-situ scanning force microscopy (SFM) uncovers elementary dynamic processes of structural rearrangements on time scales not accessible so far. Short-term interfacial undulations and the formation of transient phases (spheres, perforated lamellae, and lamellae) are observed. We demonstrate that the well-known structural defects are annihilated by short-term phase transitions into what may be considered excited states. These temporary phase transitions are reproduced in simulations based on dynamic self-consistent field theory. We discuss the role of the observed structural evolution in the context of the equilibrium phase behavior in SB thin films.

Mechanism of the transition between lamellar and gyroid phases formed by a diblock copolymer in aqueous solution.

The mechanism of the transition from a lamellar phase to a gyroid phase in an aqueous solution of a diblock copolymer has been studied by time-resolved synchrotron small-angle X-ray scattering. The transition occurs via a metastable perforated lamellar structure. The perforations initially have liquidlike ordering before developing hexagonal packing. The transient phase of irregularly perforated layers is revealed by the development of diffuse scattering peaks, just below the Bragg peaks of the lamellar structure. The diffuse scattering is modeled by Monte Carlo simulations of perforated layers. Following the formation of perforations, Bragg peaks characteristic of a hexagonal structure signal an ordering into a hexagonal lattice (with the concomitant loss of diffuse scattering). Computer simulations based on a dynamic density functional model reproduce these features. The hexagonal perforated lamellar phase is rapidly replaced by the gyroid phase. The domain spacing of the gyroid phase is larger than that of the perforated lamellar structure. The perforated lamellar and gyroid phases coexist for a defined period. The reverse transition from gyroid to lamellae occurs directly, with no transient or metastable intermediates.