Biomedical subjects

Alex H de Vries

Publications and source records attributed to Alex H de Vries.

8 recordsLinked to original sources

PubMed2006

On the decrease in lateral mobility of phospholipids by sugars.

Upon cold and drought stress, sucrose and trehalose protect membrane structures from fusion and leakage. Similarly, these sugars protect membrane proteins from inactivation during dehydration. We studied the interactions between sugars and phospholipid membranes in giant unilamellar vesicles with the fluorescent lipid analog 3,3'-dioctadecyloxacarbocyanine perchlorate incorporated. Using fluorescence correlation spectroscopy, it was found that sucrose decreased the lateral mobility of phospholipids in the fully rehydrated, liquid crystalline membrane more than other sugars did, including trehalose. To describe the nature of the difference in the interaction of phospholipids with sucrose and trehalose, atomistic molecular dynamics studies were performed. Simulations up to 100 ns showed that sucrose interacted with more phospholipid headgroups simultaneously than trehalose, resulting in a larger decrease of the lateral mobility. Using coarse-grained molecular dynamics, we show that this increase in interactions can lead to a relatively large decrease in lateral phospholipid mobility.

Carbocyanines↗

PubMed2006

Does isoprene protect plant membranes from thermal shock? A molecular dynamics study.

The question of why plants release isoprene when heat stressed has been continuously debated for more than half a century. In this work we use molecular dynamics simulation techniques to directly investigate the interaction between isoprene and a model phospholipid membrane in atomic detail. It is found that isoprene partitions preferentially in the center of the membrane and in a dose dependent manner enhances the order within the membrane without significantly changing the dynamical properties of the system. At a concentration of 20 mol% isoprene (16 isoprene molecules per 64 lipid molecules) the effect of the addition of isoprene on the membrane order is equivalent to a reduction in temperature of 10 K, rising to a reduction of 30 K at 43 mol% isoprene. The significance of the work is that it provides for the first time direct evidence that isoprene stabilizes lipid membranes and reduces the likelihood of a phospholipid membrane undergoing a heat induced phase transition. Furthermore it provides a clear mechanistic picture as to why plants specifically utilize isoprene for this purpose.

Butadienes↗

PubMed2006

Configurational entropies of lipids in pure and mixed bilayers from atomic-level and coarse-grained molecular dynamics simulations.

Single-chain and single-fragment configurational entropies of lipid tails in hydrated lipid bilayers are evaluated from molecular dynamics simulations using the quasi-harmonic approximation. The entropy distribution along individual acyl tails is obtained and compared to that of corresponding hydrocarbon chains in the liquid phase. We consider pure dipalmitoylphosphatidylcholine and mixed dioleoylphosphatidylcholine/dioleoylphosphatidylethanolamine bilayers. The systems are modeled at different levels of spatial resolution: In an atomic-level (AL) model all (heavy) atoms are explicitly simulated; in a coarse-grained (CG) model particles (beads) representing groups of covalently bound atoms are used, which map approximately four non-hydrogen atoms to one interaction site. Single-chain and single-fragment entropies and correlations between the motions of (single) acyl chains are compared. A good correspondence is found between the flexibility of the AL and CG models. The loss in configurational entropy due to the reduction in the number of degrees of freedom upon coarse-graining of the model is estimated. The CG model shows about 4 times faster convergence of the chain entropies than the more detailed AL model. Corrections to the quasi-harmonic entropy estimates were found to be small for the CG model. For the AL model, the correction due to mode anharmonicities is small, but the correction due to pairwise (supralinear) mode correlations is sizable.

Computer Simulation↗

PubMed2006

Comparison of atomic-level and coarse-grained models for liquid hydrocarbons from molecular dynamics configurational entropy estimates.

Molecular liquids can be modeled at different levels of spatial resolution. In atomic-level (AL) models, all (heavy) atoms can be explicitly simulated. In coarse-grained (CG) models, particles (beads) that represent groups of covalently bound atoms are used as elementary units. Ideally, a CG model should reproduce the thermodynamic and structural properties of the corresponding AL model after mapping to the lower-resolution scale. In the present work, two such models are investigated: (i) the classical GROMOS atomic-level model; (ii) a CG model recently proposed by Marrink et al., which maps approximately four non-hydrogen atoms to one bead [J. Phys. Chem. B 2004, 108, 750]. The study is restricted to n-alkanes whose aliphatic fragments are abundantly found in lipids of biological interest. Additionally, cis-9-octadecene is included, as a template chain of the lipid dioleoylphosphatidylcholine (DOPC). The two representations of molecules in the liquid phase are compared in terms of average molecular structures, extent of configurational space sampled, and single-molecule entropies. An approximate method is used to estimate the rotational contributions to the absolute configurational entropy. Good correspondence between the AL and CG representations is found. The loss in configurational entropy due to the reduction in degrees of freedom upon coarse-graining of the model is estimated.

Algorithms↗

PubMed2005

Molecular dynamics simulations of phospholipid bilayers: Influence of artificial periodicity, system size, and simulation time.

This article investigates the convergence of structural and dynamical properties with system size and with time in molecular dynamics simulations of solvated phospholipid bilayers performed at constant volume under periodic boundary conditions using lattice-sum electrostatics. The electron density profile across the bilayer, the carbon-deuterium order parameters, and the surface tension are shown to be converged for a bilayer containing 36 lipids per leaflet and simulated over a period of 3-4 ns. Reasonable estimates for these properties can already be obtained from a system containing 16 lipids per leaflet. The convergence limit of 36 lipids per leaflet and the investigation of the correlation between lipid headgroup dipoles suggest a correlation length of about 3-5 nm in the lateral directions for a hydrated DPPC bilayer in the liquid-crystalline phase. Although these (relatively small) system sizes and (relatively short) time scales appear sufficient to obtain converged collective structural properties at constant volume, two restrictions should be kept in mind: (i) the relaxation times associated with the motion of individual lipids may be much longer and (ii) simulated properties converge significantly faster under constant volume conditions as compared to constant pressure conditions. Therefore, an accurate assessment of the dynamical properties of the system or of the relaxation of the bilayer under constant pressure conditions may require longer simulation time scales.

Computer Simulation↗

PubMed2005

Molecular structure of the lecithin ripple phase.

Molecular dynamics simulations of lecithin lipid bilayers in water as they are cooled from the liquid crystalline phase show the spontaneous formation of rippled bilayers. The ripple consists of two domains of different length and orientation, connected by a kink. The organization of the lipids in one domain of the ripple is found to be that of a splayed gel; in the other domain the lipids are gel-like and fully interdigitated. In the concave part of the kink region between the domains the lipids are disordered. The results are consistent with the experimental information available and provide an atomic-level model that may be tested by further experiments.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2004

Lipid-mediated light activation of a mechanosensitive channel of large conductance.

This paper describes the reversible activation of a mechanosensitive channel via a light-sensitive lipid mimic. For these experiments, the mechanosensitive channel of large conductance (MscL) protein from Lactococcus lactis and Escherichia coli was reconstituted in lipid bilayers composed of 80 mol % 1,2-dioleoyl-sn-glycero-3-phosphocholine and 20 mol % di-(5-[[4-(4-butylphenyl)azo]phenoxy]pentyl)phosphate (4-Azo-5P). Light-induced isomerization of the azobenzene moiety of 4-Azo-5P from trans to cis was used to activate MscL.

Azo Compounds↗

PubMed2004

Molecular dynamics simulation of the spontaneous formation of a small DPPC vesicle in water in atomistic detail.

Molecular dynamics simulations have been used to study the spontaneous aggregation of a concentrated solution of dipalmitoylphosphatidylcholine (DPPC) molecules in water into a small vesicle. The molecules were represented in atomistic detail. Starting from a DPPC solution in water, an oblong vesicle with a long axis of 15 nm and short axes of 10 nm was formed spontaneously. After 90 ns of simulation, the vesicle contained a number of water pores. Water pores were shown to facilitate exchange of lipids between inner and outer leaflets. Lipid tails were shown to be less ordered in the inner leaflet of the vesicle, as compared to those in the outer leaflet of the vesicle and an equilibrated lamellar bilayer.

1,2-Dipalmitoylphosphatidylcholine↗