Biomedical subjects

Christian Holm

Publications and source records attributed to Christian Holm.

13 recordsLinked to original sources

PubMed2006

Osmotic coefficients of atomistic NaCl (aq) force fields.

Solvated ions are becoming increasingly important for (bio)molecular simulations. But there are not much suitable data to validate the intermediate-range solution structure that ion-water force fields produce. We compare six selected combinations of four biomolecular Na-Cl force fields and four popular water models by means of effective ion-ion potentials. First we derive an effective potential at high dilution from simulations of two ions in explicit water. At higher ionic concentration multibody effects will become important. We propose to capture those by employing a concentration dependent dielectric permittivity. With the so obtained effective potentials we then perform implicit solvent simulations. We demonstrate that our effective potentials accurately reproduce ion-ion coordination numbers and the local structure. They allow us furthermore to calculate osmotic coefficients that can be directly compared with experimental data. We show that the osmotic coefficient is a sensitive and accurate measure for the effective ion-ion interactions and the intermediate-range structure of the solution. It is therefore a suitable and useful quantity for validating and parametrizing atomistic ion-water force fields.

Journal Article↗

PubMed2006

Modeling multibody effects in ionic solutions with a concentration dependent dielectric permittivity.

We report a new strategy to parametrize effective ion-ion potentials for implicit solvent simulations of charged systems. The effective potential includes a pair term and a Coulomb term that by means of a concentration dependent dielectric permittivity takes into account multibody effects. We demonstrate that this approach allows us to accurately reproduce the solution osmotic properties and the ion coordination up to concentrations of 2.8 M aqueous NaCl.

Journal Article↗

PubMed2006

Optimal cell approach to osmotic properties of finite stiff-chain polyelectrolytes.

We propose a self-consistent geometry optimized cell model approach to study osmotic properties of stiff-chain polyelectrolyte solutions. In contrast with the usual monotonic Poisson-Boltzmann prediction, the cell model predicts the correct nonmonotonic dependence of the osmotic coefficient on concentration. A lower degree of polymerization is found to reduce significantly the counterion condensation in a typical dilute strong polyelectrolyte. The results agree quantitatively with simulations of a corresponding many-body bulk system up to a dense semidilute regime.

Electrolytes↗

PubMed2006

Spatial distribution of polyelectrolyte and counterions in nanocapsules: a computer simulation study.

We study a spatial distribution of polyelectrolyte chains and counterions inside nanometer-size capsules by means of molecular dynamics simulation on the level of a colloidal model in which polyelectrolyte coils are modeled as soft charged spheres. The capsule shell is treated as a semipermeable membrane, impermeable for the polyelectrolyte chains, but allowing free diffusion of solvent molecules and counterions. As a result, counterions leak out from the capsule immersed into a fluid of low ionic strength. This counterion leakage leads to a formation of characteristic polyelectrolyte density profiles with the central plateau and large peaks at the wall. We show that a nonuniform distribution of the inner polyelectrolyte depends on the capsule radius, surface charge, concentration of encapsulated polyelectrolyte, and the volume fraction of capsules.

Adsorption↗

PubMed2006

Interleukin-21 mRNA expression during virus infections.

Interleukin-21 is a cytokine with profound impact on the proliferation and differentiation of activated leukocytes of both the innate and adaptive immune system. In experiments in vitro, antigen activation induces IL-21 production in CD4+ T cells. Where, when, and how the proliferative and activational effects of IL-21 on different leukocytes come into play in vivo in an immune response has so far not been fully investigated. We show here for the first time in vivo, that IL-21 mRNA is produced in the spleen when mice are challenged with herpes simplex virus type 2 (HSV-2) or lymphocytic choriomeningitis virus (LCMV). We show in HSV-2 challenged mice that this production takes place in CD4+ T cell fractions and is absent in CD4+ T cell-depleted fractions. We also show that the peak of IL-21 mRNA production in both the HSV-2 and LCMV-challenged mice coincides with the onset of the adaptive immune response. Thus, our data suggest a role for IL-21 in the early stages of adaptive immune response against virus infections.

Animals↗

PubMed2005

MMM1D: a method for calculating electrostatic interactions in one-dimensional periodic geometries.

We present a new method to accurately calculate the electrostatic energy and forces on charges in a system with periodic boundary conditions in one of three spatial dimensions. We transform the Coulomb sum via a convergence factor into a series of fast decaying functions similar to the Lekner method. Rigorous error bounds for the energies and the forces are derived and numerically verified. The method has a computational complexity of O(N(2)), but is faster and easier to use than previously reported methods.

Journal Article↗

PubMed2005

Incorporation of excluded-volume correlations into Poisson-Boltzmann theory.

We investigate the effect of excluded-volume interactions on the electrolyte distribution around a charged macroion. First, we introduce a criterion for determining when hard-core effects should be taken into account beyond standard mean-field Poisson-Boltzmann (PB) theory. Next, we demonstrate that several commonly proposed local-density-functional approaches for excluded-volume interactions cannot be used for this purpose. Instead, we employ a nonlocal excess free energy by using a simple constant-weight approach. We compare the ion distribution and osmotic pressure predicted by this theory with Monte Carlo simulations. They agree very well for weakly developed correlations and give the correct layering effect for stronger ones. In all investigated cases our simple weighted-density theory yields more realistic results than the standard PB approach, whereas all local density theories do not improve on the PB density profiles, but on the contrary, deviate even more from the simulation results.

Journal Article↗

PubMed2005

Swelling of polyelectrolyte networks.

Employing molecular dynamics simulations of a coarse-grained model, the equilibrium swelling behavior of a cross-linked polyelectrolyte gel has been investigated with a bead-spring defect-free network with diamond-like topology under good solvent conditions and close to the theta-point, the counterions were treated explicitly. To examine the validity range of simple scaling arguments we varied the amount of charges in the system, the length of the network chains, the strength of the electrostatic interactions for both solvent qualities over a wide range of parameters. We find that classical theories only apply in the limit of weak electrostatics and suggest corrections based on the microscopic interplay of the systems' components accessible in a simulation, which model successfully our measured data.

Journal Article↗

PubMed2004

Screening of spherical colloids beyond mean field: a local density functional approach.

We study the counterion distribution around a spherical macroion and its osmotic pressure in the framework of the recently developed Debye-Hückel-hole-cavity (DHHC) theory. This is a local density functional approach which incorporates correlations into Poisson-Boltzmann theory by adding a free energy correction based on the one-component plasma. We compare the predictions for ion distribution and osmotic pressure obtained by the full theory and by its zero temperature limit with Monte Carlo simulations. They agree excellently for weakly developed correlations and give the correct trend for stronger ones. In all investigated cases the DHHC theory and its computationally simpler zero temperature limit yield better results than the Poisson-Boltzmann theory.

Journal Article↗

PubMed2004

Applying the chain formation model to magnetic properties of aggregated ferrofluids.

The magnetization properties of aggregated ferrofluids are calculated by combining the chain formation model developed by Zubarev with the modified mean-field theory. Using moderate assumptions for the inter- and intrachain interactions we obtain expressions for the magnetization and initial susceptibility. When comparing the results of our theory to molecular dynamics simulations of the same model we find that at large dipolar couplings (lambda>3) the chain formation model appears to give better predictions than other analytical approaches. This supports the idea that chain formation is an important structural ingredient of strongly interacting dipolar particles.

Journal Article↗

PubMed2003

Structure and magnetic properties of polydisperse ferrofluids: a molecular dynamics study.

We study by Langevin molecular dynamics simulations systematically the influence of polydispersity in the particle size, and subsequently in the dipole moment, on the physical properties of ferrofluids. The polydispersity is in a first approximation modeled by a bidisperse system that consists of small and large particles at different ratios of their volume fractions. In the first part of our investigations the total volume fraction of the system is fixed, and the volume fraction phiL of the large particles is varied. The initial susceptibility chi and magnetization curve of the systems show a strong dependence on the value of phiL. With the increase of phiL, the magnetization M of the system has a much faster increment at weak fields, and thus leads to a larger chi. We performed a cluster analysis that indicates that this is due to the aggregation of the large particles in the systems. The average size of these clusters increases with increasing phiL. In the second part of our investigations, we fixed the volume fraction of the large particles, and increased the volume fraction phiS of the small particles in order to study their influence on the chain formation of the large ones. We found that the average aggregate size formed by large particles decreases when phiS is increased, demonstrating a significant effect of the small particles on the structural properties of the system. A topological analysis of the structure reveals that the majority of the small particles remain nonaggregated. Only a small number of them are attracted to the ends of the chains formed by large particles.

Journal Article↗

PubMed2002

Molecular dynamics study on the equilibrium magnetization properties and structure of ferrofluids.

We investigate in detail the initial susceptibility, magnetization curves, and microstructure of ferrofluids in various concentration and particle dipole moment ranges by means of molecular dynamics simulations. We use the Ewald summation for the long-range dipolar interactions, take explicitly into account the translational and rotational degrees of freedom, coupled to a Langevin thermostat. When the dipolar interaction energy is comparable with the thermal energy, the simulation results on the magnetization properties agree with the theoretical predictions very well. For stronger dipolar couplings, however, we find systematic deviations from the theoretical curves. We analyze in detail the observed microstructure of the fluids under different conditions. The formation of clusters is found to enhance the magnetization at weak fields and thus leads to a larger initial susceptibility. The influence of the particle aggregation is isolated by studying ferro-solids, which consist of magnetic dipoles frozen in at random locations but which are free to rotate. Due to the artificial suppression of clusters in ferrosolids the observed susceptibility is considerably lowered when compared to ferrofluids.

Journal Article↗

PubMed2002

Conformation of a polyelectrolyte complexed to a like-charged colloid.

We report results from a molecular dynamics simulation on the conformations of a long flexible polyelectrolyte complexed to a charged sphere, both negatively charged, in the presence of neutralizing counterions in the strong Coulomb coupling regime. The structure of this complex is very sensitive to the charge density of the polyelectrolyte. For a fully charged polyelectrolyte the polymer forms a dense two-dimensional "disk," whereas for a partially charged polyelectrolyte the monomers are spread over the colloidal surface. A mechanism involving the overcharging of the polyelectrolyte by counterions is proposed to explain the observed conformations.

Colloids↗