Biomedical subjects

A J Markvoort

Publications and source records attributed to A J Markvoort.

6 recordsLinked to original sources

PubMed2006

Vesicle shapes from molecular dynamics simulations.

Lipid bilayer membranes are known to form various structures such as large sheets or vesicles. When the two leaflets of the bilayer have an equal composition, the membrane preferentially forms a flat sheet or a spherical vesicle. However, a difference in the composition of the two leaflets may result in a curved bilayer or in a wide variety of vesicle shapes. Vesicles with different shapes have already been shown in experiments and diverse vesicle shapes have been predicted theoretically from energy minimization of continuous curves. Here we present a molecular dynamics study of the effect of small changes in the phospholipid headgroups on the spontaneous curvature of the bilayer and on the resulting vesicle shape transformations. Small asymmetries in the bilayers already result in high spontaneous curvature and large vesicle deformations. Vesicle shapes that are formed include ellipsoids, discoids, pear-shaped vesicles, cup-shaped vesicles, as well as budded vesicles. Comparison of these vesicles with theoretically derived vesicle shapes shows both resemblances and differences.

Algorithms↗

PubMed2006

Coarse-grained transmembrane proteins: hydrophobic matching, aggregation, and their effect on fusion.

Molecular transport between organelles is predominantly governed by vesicle fission and fusion. Unlike experimental vesicles, the fused vesicles in molecular dynamics simulations do not become spherical readily, because the lipid and water distribution is inappropriate for the fused state and spontaneous amendment is slow. Here, we study the hypothesis that enhanced transport across the membrane of water, lipids, or both is required to produce spherical vesicles. This is done by adding several kinds of model proteins to fusing vesicles. The results show that equilibration of both water and lipid content is a requirement for spherical vesicles. In addition, the effect of these transmembrane proteins is studied in bilayers and vesicles, including investigations into hydrophobic matching and aggregation. Our simulations show that the level of aggregation does not only depend on hydrophobic mismatch, but also on protein shape. Additionally, one of the proteins promotes fusion by inducing pore formation. Incorporation of these proteins allows even flat membranes to fuse spontaneously. Moreover, we encountered a novel spontaneous vesicle enlargement mechanism we call the engulfing lobe, which may explain how lipids added to a vesicle solution are quickly incorporated into the inner monolayer.

Lipid Bilayers↗

PubMed2006

A detailed look at vesicle fusion.

Many different hypotheses on the molecular mechanisms of vesicle fusion exist. Because these mechanisms cannot be readily asserted experimentally, we address the problem by a coarse-grained molecular dynamics simulations study and compare the results with the results of other techniques. The simulations performed include the fusion of small and large vesicles and exocytosis, i.e., the fusion of small vesicles with flat bilayers. We demonstrate that the stalk, the initial contact between two fusing vesicles, is initiated by lipid tails that extend spontaneously. The stalk is revealed to be composed of the contacting monolayers only, yet without hydrophobic voids. Anisotropic and radial expansion of the stalk have been theorized; we show that stalk evolution can proceed via both pathways starting from similar setups and that water triggers the transition from elongated stalk to hemifusion diaphragm.

Exocytosis↗

PubMed2005

The bilayer-vesicle transition is entropy driven.

Self-assembled bilayer membranes have a remarkable inclination to form closed shells or vesicles. This bilayer-vesicle transition has been shown experimentally and by various kinds of computer simulation techniques. Here we study this transition using coarse-grained molecular dynamics. The advantage of this simulation technique is that it allows for a detailed analysis of the transition, such as changes of the internal energy. Generally it is assumed that the bilayer-vesicle transition is driven by minimization of the edge energy. However, our simulations, which include solvent particles, show an increase in the potential energy of the system during the transition, implicating that the transition is not energy but entropy driven.

Computer Simulation↗

PubMed2005

Hybrid method coupling molecular dynamics and Monte Carlo simulations to study the properties of gases in microchannels and nanochannels.

We combine molecular dynamics (MD) and Monte Carlo (MC) simulations to study the properties of gas molecules confined between two hard walls of a microchannel or nanochannel. The coupling between MD and MC simulations is introduced by performing MD near the boundaries for accuracy and MC in the bulk because of the low computational cost. We characterize the influence of different densities and molecule sizes on the equilibrium properties of the gas in the microchannel. The effect of the particle size on the simulation results is very small in the case of a dilute gas and increases with the density. The hybrid MD-MC simulation method is validated by comparing the results for density and temperature profiles with those of pure MD and pure MC simulations. These results compare well for pure MD and pure MC, as well as hybrid MD-MC, both in the bulk and near the boundaries, when hard-sphere interactions are used. When Lennard-Jones potentials are used to accurately model the interactions between the gas and wall molecules instead, the results of pure MD simulations differ significantly from the pure MC simulations near the boundaries, but the results of the hybrid method compare well with the pure MD results near the wall, and with the pure MC and pure MD results in the middle of the channel. The hybrid method also very accurately simulates the interface between the MD and MC simulation domains. Comparisons between MD, MC, and hybrid MD-MC computational costs are outlined. The speedup when using 50% of the domain for MD simulations and 50% for MC simulations is very small compared to pure MD simulations times, but this speedup increases drastically for more realistic situations where the region near the wall is small compared to the bulk region.

Journal Article↗

PubMed2005

Molecular dynamics study of the influence of wall-gas interactions on heat flow in nanochannels.

Especially at the nanometer scale interfaces play an important role. The effect of the wettability on the solid-liquid interface has already been studied with molecular dynamics. In this paper we study the dependence of wetting on the solid-gas interface for different density gases and investigate the influence of wetting on the heat transport properties over such an interface using molecular dynamics. Subsequently we show how the flow profile of a gas flowing along a surface also depends on this wettability. These simulations show that wettability increases the conductivity of a solid to a stationary gas and decreases the flow velocity near the interface for a gas flow. These two effects influence the cooling of a solid achieved by a cold gas flowing along its surface in opposite ways. However, we show that a higher wettability has a positive net effect on the cooling, explaining experimental results that showed an increased heat cooling effect of hydrophilic over hydrophobic microchannels.

Journal Article↗