Coarse-Grained Model for Phospholipid/Cholesterol Bilayer

We construct a coarse-grained (CG) model for dipalmitoylphosphatidylcholine (DPPC)/cholesterol bilayers and apply it to large-scale simulation studies of lipid membranes. Our CG model is a two-dimensional representation of the membrane, where the individual lipid and sterol molecules are described by point-like particles. The effective intermolecular interactions used in the model are systematically derived from detailed atomic-scale molecular dynamics simulations using the Inverse Monte Carlo technique, which guarantees that the radial distribution properties of the CG model are consistent with those given by the corresponding atomistic system. We find that the coarse-grained model for the DPPC/cholesterol bilayer is substantially more efficient than atomistic models, providing a speed-up of approximately eight orders of magnitude. The results are in favor of formation of cholesterol-rich and cholesterol-poor domains at intermediate cholesterol concentrations, in agreement with the experimental phase diagram of the system. We also explore the limits of the novel coarse-grained model, and discuss the general validity and applicability of the present approach

Molecular Dynamics Study of Charged Dendrimers in Salt-Free Solution: Effect of Counterions

Polyamidoamine (PAMAM) dendrimers, being protonated under physiological conditions, represent a promising class of nonviral, nano-sized vectors for drug and gene delivery. We performed extensive molecular dynamics simulations of a generic model dendrimer in a salt-free solution with dendrimer's terminal beads positively charged. Solvent molecules as well as counterions were explicitly included as interacting beads. We find that the size of the charged dendrimer depends non-monotonically on the strength of electrostatic interactions demonstrating a maximum when the Bjerrum length equals the diameter of a bead. Many other structural and dynamic characteristics of charged dendrimers are also found to follow this pattern. We address such a behavior to the interplay between repulsive interactions of the charged terminal beads and their attractive interactions with oppositely charged counterions. The former favors swelling at small Bjerrum lengths and the latter promotes counterion condensation. Thus, counterions can have a dramatic effect on the structure and dynamics of charged dendrimers and, under certain conditions, cannot be treated implicitly

Folding and insertion thermodynamics of the transmembrane WALP peptide

The anchor of most integral membrane proteins consists of one or several helices spanning the lipid bilayer. The WALP peptide, GWW(LA)$_n$(L)WWA, is a common model helix to study the fundamentals of protein insertion and folding, as well as helix-helix association in the membrane. Its structural properties have been illuminated in a large number of experimental and simulation studies. In this combined coarse-grained and atomistic simulation study, we probe the thermodynamics of a single WALP peptide, focusing on both the insertion across the water-membrane interface, as well as folding in both water and a membrane. The potential of mean force characterizing the peptide's insertion into the membrane shows qualitatively similar behavior across peptides and three force fields. However, the Martini force field exhibits a pronounced secondary minimum for an adsorbed interfacial state, which may even become the global minimum---in contrast to both atomistic simulations and the alternative PLUM force field. Even though the two coarse-grained models reproduce the free energy of insertion of individual amino acids side chains, they both underestimate its corresponding value for the full peptide (as compared with atomistic simulations), hinting at cooperative physics beyond the residue level. Folding of WALP in the two environments indicates the helix as the most stable structure, though with different relative stabilities and chain-length dependence.Comment: 12 pages, 5 figure

Enhanced dielectrophoresis of nanocolloids by dimer formation

We investigate the dielectrophoretic motion of charge-neutral, polarizable nanocolloids through molecular dynamics simulations. Comparison to analytical results derived for continuum systems shows that the discrete charge distributions on the nanocolloids have a significant impact on their coupling to the external field. Aggregation of nanocolloids leads to enhanced dielectrophoretic transport, provided that increase in the dipole moment upon aggregation can overcome the related increase in friction. The dimer orientation and the exact structure of the nanocolloid charge distribution are shown to be important in the enhanced transport

Phase Diagram and Commensurate-Incommensurate Transitions in the Phase Field Crystal Model with an External Pinning Potential

We study the phase diagram and the commensurate-incommensurate transitions in a phase field model of a two-dimensional crystal lattice in the presence of an external pinning potential. The model allows for both elastic and plastic deformations and provides a continuum description of lattice systems, such as for adsorbed atomic layers or two-dimensional vortex lattices. Analytically, a mode expansion analysis is used to determine the ground states and the commensurate-incommensurate transitions in the model as a function of the strength of the pinning potential and the lattice mismatch parameter. Numerical minimization of the corresponding free energy shows good agreement with the analytical predictions and provides details on the topological defects in the transition region. We find that for small mismatch the transition is of first-order, and it remains so for the largest values of mismatch studied here. Our results are consistent with results of simulations for atomistic models of adsorbed overlayers

Compiling Linguistic Constraints into Finite State Automata

International audienceThis paper deals with linguistic constraints encoded in the form of (binary) tables, generally called lexicon-grammar tables. We describe a unified method to compile sets of tables of linguistic constraints into Finite State Automata. This method has been practically implemented in the linguistic platform Unitex

Size-Exclusion Chromatography Separation Reveals That Vesicular and Non-Vesicular Small RNA Profiles Differ in Cell Free Urine.

Urinary extracellular vesicles (EVs) and their RNA cargo are a novel source of biomarkers for various diseases. We aimed to identify the optimal method for isolating small (<200 nm) EVs from human urine prior to small RNA analysis. EVs from filtered healthy volunteer urine were concentrated using three methods: ultracentrifugation (UC); a precipitation-based kit (PR); and ultrafiltration (UF). EVs were further purified by size-exclusion chromatography (SEC). EV preparations were analysed with transmission electron microscopy (TEM), Western blotting, nanoparticle tracking analysis (NTA) and an Agilent Bioanalyzer Small RNA kit. UF yielded the highest number of particles both before and after SEC. Small RNA analysis from UF-concentrated urine identified two major peaks at 10-40 nucleotides (nt) and 40-80 nt. In contrast, EV preparations obtained after UC, PR or SEC combined with any concentrating method, contained predominantly 40-80 nt sized small RNA. Protein fractions from UF+SEC contained small RNA of 10-40 nt in size (consistent with miRNAs). These data indicate that most of the microRNA-sized RNAs in filtered urine are not associated with small-sized EVs, and highlights the importance of removing non-vesicular proteins and RNA from urine EV preparations prior to small RNA analysis

Phase diagram of pinned lattices in the phase field crystal model

We study the phase diagram and the commensurate-incommensurate phase transitions of a two-dimensional phase field crystal model for adsorbed layers. The model allows for both elastic and plastic deformations on atomic and diffusive time-scales, and provides a continuum description of lattice systems, such as adsorbed atomic layers or two-dimensional vortex lattices. Analytically, mode expansion analysis and numerical minimization of the free energy are used to determine the ground states as a function of the pinning potential and lattice mismatch parameter. The results show a rich phase diagram with several different types of commensurate and incommensurate phases.Peer reviewe

Dielectrophoresis of nanocolloids: a molecular dynamics study

Dielectrophoresis (DEP), the motion of polarizable particles in non-uniform electric fields, has become an important tool for the transport, separation, and characterization of microparticles in biomedical and nanoelectronics research. In this article we present, to our knowledge, the first molecular dynamics simulations of DEP of nanometer-sized colloidal particles. We introduce a simplified model for polarizable nanoparticles, consisting of a large charged macroion and oppositely charged microions, in an explicit solvent. The model is then used to study DEP motion of the particle at different combinations of temperature and electric field strength. In accord with linear response theory, the particle drift velocities are shown to be proportional to the DEP force. Analysis of the colloid DEP mobility shows a clear time dependence, demonstrating the variation of friction under non-equilibrium. The time dependence of the mobility further results in an apparent weak variation of the DEP displacements with temperature