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.

Controlled Differentiation of Human Neural Progenitor Cells on Molybdenum Disulfide/Graphene Oxide Heterojunction Scaffolds by Photostimulation.

Ultrathin MoS2-MoO3-x heterojunction nanosheets with unique features were introduced as biocompatible, non-cytotoxic, and visible light-sensitive stimulator layers for the controlled differentiation of human neural progenitor cells (hNPCs) into nervous lineages. hNPC differentiation was also investigated on reduced graphene oxide (rGO)-containing scaffolds, that is, rGO and rGO/MoS2-MoO3-x nanosheets. In darkness, hNPC differentiation into neurons increased on MoS2-MoO3-x by a factor of 2.7 due to the excellent biophysical cues and further increased on rGO/MoS2-MoO3-x by a factor of 4.4 due to a synergistic effect induced by the rGO. The MoO3-x domains with antioxidant activity and LSPR absorption induced p-type doping in MoS2-MoO3-x. Under photostimulation, the hNPCs on the MoS2-MoO3-x exhibited higher differentiation into glial cells by a factor of 1.4, and the decrease in photo-electron current to hNPCs due to the induction of more p-type doping in the MoS2-MoO3-x. While the increase in neuronal differentiation of hNPCs on rGO/MoS2-MoO3-x by a factor of 1.8 was ascribed to the presence of rGO as an ultrafast electron transferor which quickly transferred photogenerated electrons to hNPCs before their transfer to free radicals, these results demonstrated the promising potential of MoS2-based scaffolds for applying in the controllable repair and/or regeneration of diseases/disorders related to the nervous system.

Dimerization of Aß40 inside dipalmitoylphosphatidylcholine bilayer and its effect on bilayer integrity: Atomistic simulation at three temperatures.

Amyloid-beta (Aß) protein is related to Alzheimer disease (AD), and various experiments have shown that oligomers as small as dimers are cytotoxic. Recent studies have concluded that interactions of Aß with neuronal cell membranes lead to disruption of membrane integrity and toxicity and they play a key role in the development of AD. Molecular dynamics (MD) simulations have been used to investigate Aß in aqueous solution and membranes. We have previously studied monomeric Aß40 embedded in dipalmitoylphosphatidylcholine (DPPC) membrane using MD simulations. Here, we explore interactions of two Aß40 peptides in DPPC bilayer and its consequences on dimer distribution in a lipid bilayer and on the secondary structure of the peptides. We explored that N-terminals played an important role in dimeric Aß peptide aggregations and Aß-bilayer interactions, while C-terminals bound peptides to bilayer like anchors. We did not observe exiting of peptides in our simulations although we observed insertion of peptides into the core of bilayer in some of our simulations. So it seems that the presence of Aß on membrane surface increases its aggregation rate, and as diffusion occurs in two dimensions, it can increase the probability of interpeptide interactions. We found that dimeric Aß, like monomeric one, had the ability to cause structural destabilization of DPPC membrane, which in turn might ultimately lead to cell death in an in vivo system. This information could have important implications for understanding the affinity of Aß oligomers (here dimer) for membranes and the mechanism of Aß oligomer toxicity in AD.

Granular chain escape from a pore in a wall in the presence of particles on one side: a comparison to polymer translocation.

Escape of a granular chain from a pore in a wall in the presence of diffusing granular particles on one side of the wall is studied experimentally. The escape time shows power-law behavior as a function of the chain length (τ ∝ Nα). A Langevin dynamics simulation of a polymer chain in a similar geometry is also performed and similar results to those for a granular system are obtained. A simple scaling argument and an energetic argument (based on the Onsager principle) are introduced which explain our results very well. Experiments (simulations) show that by increasing the number of particles on one side of the wall from zero, the exponent α decreases from 2.6 ± 0.1 (3.1 ± 0.1) to about 2. Both scaling and the Onsager principle argument predict α = 2 at high particle concentration, in agreement with the experiments and simulations. In the absence of particles, the scaling predicts τ = N2.5 (in agreement with the experimental result for the granular chain) and the Onsager principle predictsτ = N3 ln N, supporting the simulation result for the polymer chain. Experiments, simulations, scaling, and the Onsager principle confirm an inverse relation between τ and the density of particles on one side of the wall.

The molecular behavior of a single ß-amyloid inside a dipalmitoylphosphatidylcholine bilayer at three different temperatures: An atomistic simulation study: Aß interaction with DPPC: Atomistic simulation.

The behavior of a single Aß40 molecule within a dipalmitoylphosphatidylcholine (DPPC) bilayer was studied by all-atom molecular dynamics simulations. The effect of membrane structure was investigated on Aß40 behavior, secondary structure, and insertion depth. Simulations were performed at three temperatures (323, 310, and 300 K) to probe three different bilayer fluidities. Results show that at all above temperatures, the peptide contains two short helices, coil, bend, and turn structures. At 300 K, the peptide contains a region with ß structure in C-terminal region. Our results also show that Aß decreases the bilayer thickness and the order of lipids in its vicinity which leads to water insertion into the bilayer and concomitant increase in the local fluidity. The peptide remains embedded in the bilayer at all temperatures, and become inserted into the bilayer up to several residues at 323 and 310 K. At 310 and 300 K, the dominant interaction energy between Aß and bilayer changes from electrostatic to van der Waals. It can be proposed that at higher temperatures (e.g., 323 K), Lys28 and the C-terminal region of the peptide play the role of two anchors that keep Aß inside the top leaflet. This study demonstrates that Aß molecule can perturb the integrity of cellular membranes. Proteins 2017; 85:1298-1310. © 2017 Wiley Periodicals, Inc.

Obstruction enhances the diffusivity of self-propelled rod-like particles.

Diffusion of self-propelled particles in the presence of randomly distributed obstacles is studied in three dimensions (3D) using Langevin dynamics simulations. It is found that depending on the magnitude of the propelling force and the particle aspect ratio, the diffusion coefficient can be a monotonically decreasing or a non-monotonic concave function of the obstructed volume fraction. Counterintuitive enhancement of the particle diffusivity with increasing the obstacle crowd is shown to be resulted from interplay of self-propulsion and anisotropy in the particle shape. On the propelling force-aspect ratio plane, regions that correspond to monotonic and non-monotonic dependence of the diffusivity on obstacle density are specified using the simulation results and the boundary between the two regions is described.

A flexible polymer confined inside a cone-shaped nano-channel.

The nano-scale confinement of polymers in cone-shaped geometries occurs in many experimental situations. A flexible polymer confined in a cone-shaped nano-channel is studied theoretically and by using molecular dynamics simulations. Distribution of the monomers inside the channel, configuration of the confined polymer, the entropic force acting on the polymer, and their dependence on the channel and the polymer parameters are investigated. The theory and the simulation results are in very good agreement. The entropic force on the polymer that results from the asymmetric shape of the channel is measured in the simulations and its magnitude is found to be significant relative to thermal energy. The obtained dependence of the force on the channel parameters may be useful in the design of cone-shaped nano-channels.

Mechanisms of the self-assembly of EAK16-family peptides into fibrillar and globular structures: molecular dynamics simulations from nano- to micro-seconds.

The self-assembly of EAK16-family peptides in a bulk solution was studied using a combination of all-atom and coarse-grained molecular dynamics simulations. In addition, specified concentrations of EAK16 peptides were induced to form fibrillary or globular assemblies in vitro. The results show that the combination of all-atom molecular dynamics simulations on the single- and double-chain levels and coarse-grained simulations on the many-chain level predicts the experimental observations reasonably well. At neutral pH conditions, EAK16-I and EAK16-II assemble into fibrillary structures, whereas EAK16-IV aggregates into globular assemblies. Mechanisms of the formation of fibrillar and globular assemblies are described using the simulation results.

pH-dependent self-assembly of EAK16 peptides in the presence of a hydrophobic surface: coarse-grained molecular dynamics simulation.

Self-assembly behavior of the three types of ionic peptide, EAK16, is studied in the presence of a hydrophobic surface using coarse-grained molecular dynamics simulations at three pH ranges of the solution. It is found that the peptide chains of all the three types assemble on the hydrophobic surface. EAK16-I and EAK16-II peptides assemble into ribbon-like structures, regardless of the value of pH. EAK16-IV peptide chains, however, assemble into ribbon-like structures at low and high pH ranges and form disc-shaped assemblies on the hydrophobic surface at the isoelectric point, pH = 7. Strong intra-chain electrostatic interactions in the case of EAK16-IV peptide play the main role in dependence of its self-assembly behavior on pH and the different morphology of its assembly relative to those of the two other types. Kinetics of growth of the assemblies on the hydrophobic surface is also studied.

All-atom molecular dynamics study of EAK16 peptide: the effect of pH on single-chain conformation, dimerization and self-assembly behavior.

Single-chain equilibrium conformation and dimerization of the three types of ionic EAK16 peptide are studied under three pH conditions using all-atom molecular dynamics simulations. It is found that both the single-chain conformation and the dimerization process of EAK16-IV are considerably different from those of the two other types, EAK16-I and EAK16-II. The value of pH is found to have a stronger effect on the single-chain conformation and dimerization of EAK16-IV. It is shown that in addition to the charge pattern on the peptide chains, the size of the side chains of the charged amino acids plays role in the conformation of the peptide chains and their dimerization. The results shed light on the pH-dependent self-assembly behavior of EAK16 peptide in the bulk solution, which has been reported in the literature.

Directed translocation of a flexible polymer through a cone-shaped nano-channel.

Translocation of a flexible polymer through a cone-shaped channel is studied, theoretically and using computer simulations. Our simulations show that the shape of the channel causes the polymer translocation to be a driven process. The effective driving force of entropic origin acting on the polymer is calculated as a function of the length and the apex-angle of the channel, theoretically. It is found that the translocation time is a non-monotonic function of the apex-angle of the channel. By increasing the apex-angle from zero, the translocation time shows a minimum and then a maximum. Also, it is found that regardless of the value of the apex-angle, the translocation time is a uniformly decreasing function of the channel length. The results of the theory and the simulation are in good qualitative agreement.

Association between Y-chromosome AZFc region micro-deletions with recurrent miscarriage.

BACKGROUND: In human, about 25% of implanted embryos are losing 1-2 week following attachment to the uterus. A subset of this population will have three or more consecutive miscarriages which define as repeated pregnancy loss (RPL). Introducing the assisted reproductive technologies (ARTS) made a chance for infertile couples to solve their childless problem. OBJECTIVE: This study was conducted to evaluate the incidence of Y-chromosome AZF region's micro-deletions in male partners of couples with recurrent miscarriage (RM). MATERIALS AND METHODS: Thirty male partner of couples with RM and thirty infertile males, who referred to the Yazd Research and Clinical Center for Infertility were recruited to this study. In addition, 30 healthy men were screened as a control group from the same center. After DNA extraction using salting out method, the multiplex-PCR was done for amplifying 8 known STSs proximal to the AZF region of the Y-chromosome. The results were compared between the groups using Fisher's exact t-test and p<0.05 was considered statistically significant. RESULTS: Of the 30 infertile males, 5 (16.6%) cases were associated with the AZF region micro-deletions of DYF87S, DYF84S1, DYF83S1 and DYF51S1, STSs. But in the fertile and RM male groups was found no deletions similar to those, of the infertile males (p=1.0). Instead 4 (13.3%) cases of the RM group males had different micro-deletions included DYS220 (AZFb, sY129), DYS262, DYF8551, and DYF8651, STSs. The AZFc locus of Y-chromosome micro-deletions have a significant role in RM (p=0.045). CONCLUSION: It seems that the Y-chromosome AZF region's micro-deletions are associated with RM, and we recommend adding this AZF region STSs into infertility analyzing panels.

Distribution of counterions and interaction between two similarly charged dielectric slabs: roles of charge discreteness and dielectric inhomogeneity.

The distribution of counterions and the electrostatic interaction between two similarly charged dielectric slabs is studied in the strong coupling limit. Dielectric inhomogeneities and discreteness of charge on the slabs have been taken into account. It is found that the amount of dielectric constant difference between the slabs and the environment, and the discreteness of charge on the slabs have opposing effects on the equilibrium distribution of the counterions. At small interslab separations, increasing the amount of dielectric constant difference increases the tendency of the counterions toward the middle of the intersurface space between the slabs and the discreteness of charge pushes them to the surfaces of the slabs. In the limit of point charges, independent of the strength of dielectric inhomogeneity, counterions distribute near the surfaces of the slabs. The interaction between the slabs is attractive at low temperatures and its strength increases with the dielectric constant difference. At room temperature, the slabs may completely attract each other, reach to an equilibrium separation, or have two equilibrium separations with a barrier in between, depending on the system parameters.

Electric-field-driven polymer entry into asymmetric nanoscale channels.

The electric-field-driven entry process of flexible charged polymers such as single-stranded DNA (ssDNA) into asymmetric nanoscale channels such as the α-hemolysin protein channel is studied theoretically and using molecular dynamics simulations. Dependence of the height of the free-energy barrier on the polymer length, the strength of the applied electric field, and the channel entrance geometry is investigated. It is shown that the squeezing effect of the driving field on the polymer and the lateral confinement of the polymer before its entry to the channel crucially affect the barrier height and its dependence on the system parameters. The attempt frequency of the polymer for passing the channel is also discussed. Our theoretical and simulation results support each other and describe related data sets of polymer translocation experiments through the α-hemolysin protein channel reasonably well.

Free-energy barrier for electric-field-driven polymer entry into nanoscale channels.

Free-energy barrier for entry of a charged polymer into a nanoscale channel by a driving electric field is studied theoretically and using molecular dynamics simulations. Dependence of the barrier height on the polymer length, the driving field strength, and the channel entrance geometry is investigated. Squeezing effect of the electric field on the polymer before its entry to the channel is taken into account. It is shown that lateral confinement of the polymer prior to its entry changes the polymer length dependence of the barrier height noticeably. Our theory and simulation results are in good agreement and reasonably describe related experimental data.

Three-dimensional Brownian diffusion of rod-like macromolecules in the presence of randomly distributed spherical obstacles: molecular dynamics simulation.

Brownian diffusion of rod-like polymers in the presence of randomly distributed spherical obstacles is studied using molecular dynamics simulations. It is observed that dependence of the reduced diffusion coefficient of these macromolecules on the available volume fraction can be described reasonably by a power law function. Despite the case of obstructed diffusion of flexible polymers in which reduced diffusion coefficient has a weak dependence on the polymer length, this dependence is noticeably strong in the case of rod-like polymers. Diffusion of these macromolecules in the presence of obstacles is observed that is anomalous at short time scales and normal at long times. Duration time of the anomalous diffusion regime is found that increases very rapidly with increasing both the polymer length and the obstructed volume fraction. Dynamics of diffusion of these polymers is observed that crosses over from Rouse to reptation type with increasing the density of obstacles.

Brushes of flexible, semiflexible, and rodlike diblock polyampholytes: Molecular dynamics simulation and scaling analysis.

Planar brushes of flexible, semiflexible, and rodlike diblock polyampholytes are studied using molecular dynamics simulations in a wide range of the grafting density. Simulations show linear dependence of the average thickness on the grafting density in all cases regardless of different flexibility of anchored chains and the brushes' different equilibrium conformations. Slopes of fitted lines to the average thickness of the brushes of semiflexible and rodlike polyampholytes versus the grafting density are approximately the same and differ considerably from that of the brushes of flexible chains. The average thickness of the brush of flexible diblock polyampholytes as a function of the grafting density is also obtained using a simple scaling analysis, which is in good agreement with our simulations.

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.

Aggregation kinetics of stiff polyelectrolytes in the presence of multivalent salt.

Using molecular dynamics simulations, the kinetics of bundle formation for stiff polyelectrolytes such as actin is studied in the solution of multivalent salt. The dominant kinetic mode of aggregation is found to be the case of one end of one rod meeting others at a right angle due to electrostatic interactions. The kinetic pathway to bundle formation involves a hierarchical structure of small clusters forming initially and then feeding into larger clusters, which is reminiscent of the flocculation dynamics of colloids. For the first few cluster sizes, the Smoluchowski formula for the time evolution of the cluster size gives a reasonable account of the results of our simulation without a single fitting parameter. The description using the Smoluchowski formula provides evidence for the aggregation time scale to be controlled by diffusion, with no appreciable energy barrier to overcome.

Orientational ordering and dynamics of rodlike polyelectrolytes.

The interplay between electrostatic interactions and orientational correlations is studied for a model system of charged rods positioned on a chain, using Monte Carlo simulation techniques. It is shown that the coupling brings about the notion of electrostatic frustration, which in turn results in: (i) a rich variety of orientational orderings such as chiral phases, and (ii) an inherently slow dynamics characterized by stretched-exponential behavior in the relaxation functions of the system.