Impact of flexibility on the aggregation of polymeric macromolecules.

Dependence of the dimerization probability and the aggregation behavior of polymeric macromolecules on their flexibility is studied using Langevin dynamics simulations. It is found that the dimerization probability is a non-monotonic function of the polymers persistence length. For a given value of inter-polymer attraction strength, semiflexible polymers have lower dimerization probability relative to flexible and rigid polymers of the same length. The threshold temperature of the formation of aggregates in a many-polymer system and its dependence on the polymers persistence length is also investigated. The simulation results of two- and many-polymer systems are in good agreement and show how the amount of flexibility affects the dimerization and the aggregation behaviors of polymeric macromolecules.

Stokesian dynamics simulations of a magnetotactic bacterium.

The swimming of bacteria provides insight into propulsion and steering under the conditions of low-Reynolds number hydrodynamics. Here we address the magnetically steered swimming of magnetotactic bacteria. We use Stokesian dynamics simulations to study the swimming of single-flagellated magnetotactic bacteria (MTB) in an external magnetic field. Our model MTB consists of a spherical cell body equipped with a magnetic dipole moment and a helical flagellum rotated by a rotary motor. The elasticity of the flagellum as well as magnetic and hydrodynamic interactions is taken into account in this model. We characterized how the swimming velocity is dependent on parameters of the model. We then studied the U-turn motion after a field reversal and found two regimes for weak and strong fields and, correspondingly, two characteristic time scales. In the two regimes, the U-turn time is dominated by the turning of the cell body and its magnetic moment or the turning of the flagellum, respectively. In the regime for weak fields, where turning is dominated by the magnetic relaxation, the U-turn time is approximately in agreement with a theoretical model based on torque balance. In the strong-field regime, strong deformations of the flagellum are observed. We further simulated the swimming of a bacterium with a magnetic moment that is inclined relative to the flagellar axis. This scenario leads to intriguing double helical trajectories that we characterize as functions of the magnetic moment inclination and the magnetic field. For small inclination angles ([Formula: see text]) and typical field strengths, the inclination of the magnetic moment has only a minor effect on the swimming of MTB in an external magnetic field. Large inclination angles result in a strong reduction in the velocity in direction of the magnetic field, consistent with recent observations that bacteria with large inclination angles use a different propulsion mechanism.

High-speed motility originates from cooperatively pushing and pulling flagella bundles in bilophotrichous bacteria.

Bacteria propel and change direction by rotating long, helical filaments, called flagella. The number of flagella, their arrangement on the cell body and their sense of rotation hypothetically determine the locomotion characteristics of a species. The movement of the most rapid microorganisms has in particular remained unexplored because of additional experimental limitations. We show that magnetotactic cocci with two flagella bundles on one pole swim faster than 500 µm·s-1 along a double helical path, making them one of the fastest natural microswimmers. We additionally reveal that the cells reorient in less than 5 ms, an order of magnitude faster than reported so far for any other bacteria. Using hydrodynamic modeling, we demonstrate that a mode where a pushing and a pulling bundle cooperate is the only possibility to enable both helical tracks and fast reorientations. The advantage of sheathed flagella bundles is the high rigidity, making high swimming speeds possible.

Vesicle-like structure of lipid-based nanoparticles as drug delivery system revealed by molecular dynamics simulations.

Lipid-based drug delivery systems are considered as promising vehicles for hydrophobic drug compounds. Lipid distribution within the droplet can affect drug loading capacity in these carriers. However, it is extremely challenging to determine the nanostructure within these carriers through the implementation of the direct experimental methods due to the ultrafine size. Therefore, coarse grained molecular dynamics (MD) simulation was utilized to model different kinds of lipid-based nanoparticles of the diameter about 12 nm including solid lipid nanoparticles (SLN), nanoemulsion (NE), and nanostructured lipid carriers (NLC), and the organization of the lipids within the carriers was explored. The aforementioned nanoparticles consisted of stearic acid, oleic acid as lipids, and sodium dodecyl sulfate (SDS) as a surfactant in water medium. Furthermore, the impact of solid to liquid mass ratio on the lipid distribution within the lipid matrix was investigated regarding the NLC simulations. In the equilibrium state, we observed the vesicle-like structure for all the investigated systems in which the hydrophilic moieties of the lipids and surfactant organized a semi-bilayer fold into the droplet and the hydrophobic tails accumulated among them. It is worth mentioning although SDS as a harsh surfactant, which is a special case, was expected to be present in the surface of the droplet, it penetrated into the lipids. Additionally, our results showed remarkable entrapped water beads inside the droplet in the form of one or more cavities along the internal layer of the head groups which was surrounded by lipid head groups. It was also reported that in the building structure of the nanoemulsion and SLN, in the central parts of the droplets, lipids were denser than the case of NLCs. Moreover, no crystallization occurred within the lipid-based carriers. Finally, the results indicated that, in the case of NLC simulations, the lipid distribution within the lipid matrix was insensitive to the mass fraction of solid to liquid lipids.

Pore formation and the key factors in antibacterial activity of aurein 1.2 and LLAA inside lipid bilayers, a molecular dynamics study.

Aurein 1.2 and LLAA are two antimicrobial peptides with different antibacterial activities (LLAA>Aurein 1.2), though their amino acid sequences are similar. In this manuscript, we study the key features for the different antibacterial activities of these peptides using molecular dynamics simulation. We find that in water, both peptides become disordered and LLAA is observed to have higher water-solubility, a feature which may contribute to enhancing its propensity to disrupt the bilayer and thus higher activity. Both peptides are also investigated while they are initially located inside lipid bilayer as a pre-formed vertical channel composed of five parallel copies of each peptide. LLAA demonstrates larger structural deviation from the initial helical structure and also more structural flexibility which is concluded to be a key feature in its stronger activity. In the presence of LLAA, the bilayer order is perturbed more pronouncedly and the number of water molecules penetrating into bilayer is higher. It is shown that stronger electrostatic interactions, more hydrophobic contacts and more hydrogen bonds between lipid and LLAA also lead to stronger activity of LLAA. The simulation results show instability of the barrel-stave pores for our peptides inside lipid bilayers.

Interaction of aurein 1.2 and its analogue with DPPC lipid bilayer.

Antibacterial peptides have potential as novel therapeutic agents for bacterial infections. Aurein 1.2 is one of the smallest antibacterial peptides extracted from an anuran. LLAA is a more active analogue of aurein 1.2. Antibacterial peptides usually accomplish their function by interacting with bacterial membrane selectively. In this study, we tried to find the reasons for the stronger antibacterial activity of LLAA compared with aurein 1.2. For this purpose, the interaction of aurein 1.2 and LLAA with dipalmitoylphosphatidylcholine (DPPC) was investigated by molecular dynamics (MD) simulation. In addition, the structure of peptides and their antibacterial activity were investigated by circular dichroism (CD) and dilution test method, respectively. MD results showed that LLAA is more flexible compared with aurein 1.2. Furthermore, LLAA loses its structure more than aurein 1.2 in the DPPC bilayer. A higher amount of water molecules penetrate into bilayer in the presence of LLAA relative to aurein 1.2. According to the antibacterial result that indicated LLAA is remarkably more active than aurein 1.2, it can be concluded that flexibility of the peptide is a determining factor in antibacterial activity. Probably, flexibility of the peptides facilitates formation of effective pores in the lipid bilayer.

Stability of actin-lysozyme complexes formed in cystic fibrosis disease.

Finding the conditions for destabilizing actin-lysozyme complexes is of biomedical importance in preventing infections in cystic fibrosis. In this manuscript, the effects of different charge-mutants of lysozyme and salt concentration on the stability of actin-lysozyme complexes are studied using Langevin dynamics simulation. A coarse-grained model of F-actin is used in which both its twist and bending rigidities are considered. We observe that the attraction between F-actins is stronger in the presence of wild-type lysozymes relative to the mutated lysozymes of lower charges. By calculating the potential of mean force between F-actins, we conclude that the stability of actin-lysozyme complexes is decreased by reducing the charge of lysozyme mutants. The distributions of different lysozyme charge-mutants show that wild-type (+9e) lysozymes are mostly accumulated in the center of triangles formed by three adjacent F-actins, while lysozyme mutants of charges +7e and +5e occupy the bridging regions between F-actins. Low-charge mutants of lysozyme (+3e) distribute uniformly around F-actins. A rough estimate of the electrostatic energy for these different distributions proves that the distribution in which lysozymes reside in the center of triangles leads to more stable complexes. Also our results in the presence of a salt suggest that at physiological salt concentration of airway, F-actin complexes are not formed by charge-reduced mutants of lysozyme. The findings are interesting because if we can design charge-reduced lysozyme mutants with considerable antibacterial activity, they are not sequestered inside F-actin aggregates and can play their role as antibacterial agents against airway infection.

Salt-induced aggregation of stiff polyelectrolytes.

Molecular dynamics simulation techniques are used to study the process of aggregation of highly charged stiff polyelectrolytes due to the presence of multivalent salt. The dominant kinetic mode of aggregation is found to be the case of one end of one polyelectrolyte meeting others at right angles, and the kinetic pathway to bundle formation is found to be similar to that of flocculation dynamics of colloids as described by Smoluchowski. The aggregation process is found to favor the formation of finite bundles of 10-11 filaments at long times. Comparing the distribution of the cluster sizes with the Smoluchowski formula suggests that the energy barrier for the aggregation process is negligible. Also, the formation of long-lived metastable structures with similarities to the raft-like structures of actin filaments is observed within a range of salt concentration.