Atomistic Simulations of Bicelle Mixtures

AbstractMixtures of long- and short-tail phosphatidylcholine lipids are known to self-assemble into a variety of aggregates combining flat bilayerlike and curved micellelike features, commonly called bicelles. Atomistic simulations of bilayer ribbons and perforated bilayers containing dimyristoylphosphatidylcholine (DMPC, di-C14 tails) and dihexanoylphosphatidylcholine (DHPC, di-C6 tails) have been carried out to investigate the partitioning of these components between flat and curved microenvironments and the stabilization of the bilayer edge by DHPC. To approach equilibrium partitioning of lipids on an achievable simulation timescale, configuration-bias Monte Carlo mutation moves were used to allow individual lipids to change tail length within a semigrand-canonical ensemble. Since acceptance probabilities for direct transitions between DMPC and DHPC were negligible, a third component with intermediate tail length (didecanoylphosphatidylcholine, di-C10 tails) was included at a low concentration to serve as an intermediate for transitions between DMPC and DHPC. Strong enrichment of DHPC is seen at ribbon and pore edges, with an excess linear density of ∼3 nm−1. The simulation model yields estimates for the onset of edge stability with increasing bilayer DHPC content between 5% and 15% DHPC at 300 K and between 7% and 17% DHPC at 323 K, higher than experimental estimates. Local structure and composition at points of close contact between pores suggest a possible mechanism for effective attractions between pores, providing a rationalization for the tendency of bicelle mixtures to aggregate into perforated vesicles and perforated sheets

Molecular mechanistic origin of the toughness of natural adhesives, fibres and composites

Natural materials are renowned for their strength and toughness(1-5). Spider dragline silk has a breakage energy per unit weight two orders of magnitude greater than high tensile steel(1,6), and is representative of many other strong natural fibres(3,7,8). The abalone shell, a composite of calcium carbonate plates sandwiched between organic material, is 3,000 times more fracture resistant than a single crystal of the pure mineral(4,5). The organic component, comprising just a few per cent of the composite by weight(9), is thought to hold the key to nacre's fracture toughness(10,11). Ceramics laminated with organic material are more fracture resistant than non-laminated ceramics(11,12), but synthetic materials made of interlocking ceramic tablets bound by a few weight per cent of ordinary adhesives do not have a toughness comparable to nacre(13). We believe that the key to nacre's fracture resistance resides in the polymer adhesive, and here we reveal the properties of this adhesive by using the atomic force microscope(14) to stretch the organic molecules exposed on the surface of freshly cleaved nacre. The adhesive fibres elongate in a stepwise manner as folded domains or loops are pulled open. The elongation events occur for forces of a few hundred piconewtons, which are smaller than the forces of over a nanonewton required to break the polymer backbone in the threads. We suggest that this 'modular' elongation mechanism might prove to be quite general for conveying toughness to natural fibres and adhesives, and we predict that it might be found also in dragline silk

Thermodynamics and structure of self-assembled networks

We study a generic model of self-assembling chains which can branch and form networks with branching points (junctions) of arbitrary functionality. The physical realizations include physical gels, wormlike micells, dipolar fluids and microemulsions. The model maps the partition function of a solution of branched, self-assembling, mutually avoiding clusters onto that of a Heisenberg magnet in the mathematical limit of zero spin components. The model is solved in the mean field approximation. It is found that despite the absence of any specific interaction between the chains, the entropy of the junctions induces an effective attraction between the monomers, which in the case of three-fold junctions leads to a first order reentrant phase separation between a dilute phase consisting mainly of single chains, and a dense network, or two network phases. Independent of the phase separation, we predict the percolation (connectivity) transition at which an infinite network is formed that partially overlaps with the first-order transition. The percolation transition is a continuous, non thermodynamic transition that describes a change in the topology of the system. Our treatment which predicts both the thermodynamic phase equilibria as well as the spatial correlations in the system allows us to treat both the phase separation and the percolation threshold within the same framework. The density-density correlation correlation has a usual Ornstein-Zernicke form at low monomer densities. At higher densities, a peak emerges in the structure factor, signifying an onset of medium-range order in the system. Implications of the results for different physical systems are discussed.Comment: Submitted to Phys. Rev.

Enlargement of ribbons in zebrafish hair cells increases calcium currents, but disrupts afferent spontaneous activity and timing of stimulus onset.

In sensory hair cells of auditory and vestibular organs, the ribbon synapse is required for the precise encoding of a wide range of complex stimuli. Hair cells have a unique presynaptic structure-the synaptic ribbon-that organizes both synaptic vesicles and calcium channels at the active zone. Previous work has shown that hair-cell ribbon size is correlated with differences in postsynaptic activity. However, additional variability in postsynapse size presents a challenge to determining the specific role of ribbon size in sensory encoding. To selectively assess the impact of ribbon size on synapse function, we examined hair cells in transgenic zebrafish that have enlarged ribbons, without postsynaptic alterations. Morphologically, we found that enlarged ribbons had more associated vesicles and reduced presynaptic calcium-channel clustering. Functionally, hair cells with enlarged ribbons had larger global and ribbon-localized calcium currents. Afferent neuron recordings revealed that hair cells with enlarged ribbons resulted in reduced spontaneous spike rates. Additionally, despite larger presynaptic calcium signals, we observed fewer evoked spikes with longer latencies from stimulus onset. Taken together, our work indicates that hair-cell ribbon size influences the spontaneous spiking and the precise encoding of stimulus onset in afferent neurons.SIGNIFICANCE STATEMENTNumerous studies support that hair-cell ribbon size corresponds with functional sensitivity differences in afferent neurons and, in the case of inner hair cells of the cochlea, vulnerability to damage from noise trauma. Yet it is unclear whether ribbon size directly influences sensory encoding. Our study reveals that ribbon enlargement results in increased ribbon-localized calcium signals, yet reduces afferent spontaneous activity and disrupts the timing of stimulus onset-a distinct aspect of auditory and vestibular encoding. These observations suggest that varying ribbon size alone can influence sensory encoding, and give further insight into how hair cells transduce signals that cover a wide dynamic range of stimuli

Easier sieving through narrower pores: fluctuations and barrier crossing in flow-driven polymer translocation

We show that the injection of polymer chains into nanochannels becomes easier as the channel becomes narrower. This counter intuitive result arises because of a decrease in the diffusive time scale of the chains with increasing confinement. The results are obtained by extending the de Gennes blob model of confined polymers, and confirmed by hybrid molecular dynamics - lattice-Boltzmann simulations.Comment: 5 pages, 3 figure