Simulations of elementary processes in entangle wormlike micelles under tension : a kinetic pathway to Y-junctions and shear induced structures

The merging process of two amphiphilic cylindrical micelles has been simulated using a coarse grained model in which amphiphiles are represented as chains of one head particle and four tail particles. In our set-up with twisted boundary conditions, a ring-shaped worm is effectively entangled with itself. Upon stretching the box, putting the worms under tension, a fusion into an H-like structure is observed, which eventually transforms into an almost tensionless structure with two freely gliding Y-junctions. The tensions on the worms never reach the point where scission becomes an alternative to fusion. We end with a short discussion of the possible implications of these observations

Shear viscosities and normal stress differences of rigid liquid-crystalline polymers

Shear viscosities as well as first and second normal stress differences of solutions of rigid spherocylindrical colloids are investigated by Brownian dynamics simulations for aspect ratios L/D in a range from 25 to 60 and scaled volume fractions L/D from 0.5 to 4.5. Shear thinning behavior is observed in all cases. In the isotropic phase, the calculated viscosities at low volume fractions are in agreement with predictions by Dhont and Briels, while over a larger range of shear rates they are described by the Hess equation. The self-rotational diffusion coefficients obtained from the flow curves agree very well with those calculated by traditional methods. In the nematic phase, the inflection point of the flow curve is associated with the critical shear rate at which the orientational director changes its motion from kayaking to wagging. The first normal stress difference N1 in the nematic solution is positive at low and high shear rates but negative at moderate rates, which is rather distinct from the monotone behavior shown by isotropic solutions. The simulated second normal stress difference N2 is found much smaller in amplitude than N1 and always opposite in sign. Our findings qualitatively confirm existing theoretical predictions and experimental measurements. A newly developed event-driven Brownian dynamics algorithm, in which the excluded-volume interactions between particles are incorporated as collisions instead of as repulsive potentials, has made these simulations feasible

The attachment of α-synuclein to a fiber:A coarse-grain approach

We present simulations of the amyloidogenic core of α-synuclein, the protein causing Parkinson’s disease, as a short chain of coarse-grain patchy particles. Each particle represents a sequence of about a dozen amino acids. The fluctuating secondary structure of this intrinsically disordered protein is modelled by dynamic variations of the shape and interaction characteristics of the patchy particles, ranging from spherical with weak isotropic attractions for the disordered state to spherocylindrical with strong directional interactions for a β-sheet. Flexible linkers between the particles enable sampling of the tertiary structure. This novel model is applied here to study the growth of an amyloid fibril, by calculating the free energy profile of a protein attaching to the end of a fibril. The simulation results suggest that the attaching protein readily becomes trapped in a mis-folded state, thereby inhibiting further growth of the fibril until the protein has readjusted to conform to the fibril structure, in line with experimental findings and previous simulations on small fragments of other proteins

Capacitance and Structure of Electric Double Layers: Comparing Brownian Dynamics and Classical Density Functional Theory

We present a study of the structure and differential capacitance of electric double layers of aqueous electrolytes. We consider Electric Double Layer Capacitors (EDLC) composed of spherical cations and anions in a dielectric continuum confined between a planar cathode and anode. The model system includes steric as well as Coulombic ion-ion and ion-electrode interactions. We compare results of computationally expensive, but "exact", Brownian Dynamics (BD) simulations with approximate, but cheap, calculations based on classical Density Functional Theory (DFT). Excellent overall agreement is found for a large set of system parameters $-$ including variations in concentrations, ionic size- and valency-asymmetries, applied voltages, and electrode separation $-$ provided the differences between the canonical ensemble of the BD simulations and the grand-canonical ensemble of DFT are properly taken into account. In particular a careful distinction is made between the differential capacitance $C_N$ at fixed number of ions and $C_\mu$ at fixed ionic chemical potential. Furthermore, we derive and exploit their thermodynamic relations. In the future these relations are also useful for comparing and contrasting

Cancer immune therapy using engineered ‛tail-flipping’ nanoliposomes targeting alternatively activated macrophages

Alternatively-activated, M2-like tumor-associated macrophages (TAM) strongly contribute to tumor growth, invasiveness and metastasis. Technologies to disable the pro-tumorigenic function of these TAMs are of high interest to immunotherapy research. Here we show that by designing engineered nanoliposomes bio-mimicking peroxidated phospholipids that are recognised and internalised by scavenger receptors, TAMs can be targeted. Incorporation of phospholipids possessing a terminal carboxylate group at the sn-2 position into nanoliposome bilayers drives their uptake by M2 macrophages with high specificity. Molecular dynamics simulation of the lipid bilayer predicts flipping of the sn-2 tail towards the aqueous phase, while molecular docking data indicates interaction of the tail with Scavenger Receptor Class B type 1 (SR-B1). In vivo, the engineered nanoliposomes are distributed specifically to M2-like macrophages and, upon delivery of the STAT6 inhibitor (AS1517499), zoledronic acid or muramyl tripeptide, these cells promote reduction of the premetastatic niche and/or tumor growth. Altogether, we demonstrate the efficiency and versatility of our engineered “tail-flipping” nanoliposomes in a pre-clinical model, which paves the way to their development as cancer immunotherapeutics in humans

Molecular dynamics simulations of barrier crossings in the condensed phase

The isomerisation rates of a calix[4]arene in vacuo and in two solvents have been computed by means of molecular dynamics simulations (MD). In MD the equations of classical mechanics are used to calculate the motion of the reacting molecule and the surrounding solvent molecules. Thus, the intricate influence of the solvent on the reacting molecule is realistically accounted for. Unfortunately, MD simulations are computationally very demanding because of the large number of non-bonded interactions between the molecules, and the rapid internal motions of the molecules which make it necessary to calculate the interactions at femtosecond intervals. During an isomerisation reaction a molecule goes from one energetically favourable conformation to another energetically favourable conformation without breaking or forming covalent bonds. Such events are rare on the time scale of the normal dynamics of the molecule, i. e. the motion within a low energy region, since during the reaction the molecule has to pass through an energetically unfavourable region. In MD simulations of the isomerisation of a calix[4]arene in a solvent, with an experimental rate constant of about 100 s-1, a reaction event occurs roughly once every 100,000 CPU-years

Free energies of stable and metastable pores in lipid membranes under tension

The free energy profile of pore formation in a lipid membrane, covering the entire range from a density fluctuation in an intact bilayer to a large tension-stabilized pore, has been calculated by molecular dynamics simulations with a coarse-grained lipid model. Several fixed elongations are used to obtain the Helmholtz free energy as a function of pore size for thermodynamically stable, metastable, and unstable pores, and the system-size dependence of these elongations is discussed. A link to the Gibbs free energy at constant tension, commonly known as the Litster model, is established by a Legendre transformation. The change of genus upon pore formation is exploited to estimate the saddle-splay modulus or Gaussian curvature modulus of the membrane leaflets. Details are provided of the simulation approach, which combines the potential of mean constraint force method with a reaction coordinate based on the local lipid density