Biomedical subjects

Michael Patra

Publications and source records attributed to Michael Patra.

11 recordsLinked to original sources

PubMed2006

Simulation of grafted polymers on nanopatterned surfaces.

Structural properties of polymer brushes on nanopatterned surfaces in good solvent have been determined by computer simulations. Scaling relations for the brush height and brush width are proposed. The properties of the central part of the patterned brush remain constant as long as the pattern is wider than a few times the brush height. The results agree qualitatively with recent AFM experiments, but some quantitative differences call for a reassessment of experimental procedures.

Journal Article↗

PubMed2005

Under the influence of alcohol: the effect of ethanol and methanol on lipid bilayers.

Extensive microscopic molecular dynamics simulations have been performed to study the effects of short-chain alcohols, methanol and ethanol, on two different fully hydrated lipid bilayer systems (POPC and DPPC) in the fluid phase at 323 K. It is found that ethanol has a stronger effect on the structural properties of the membranes. In particular, the bilayers become more fluid and permeable: ethanol molecules are able to penetrate through the membrane in typical timescales of approximately 200 ns, whereas for methanol that timescale is considerably longer, at least of the order of microseconds. A closer examination exposes a number of effects due to ethanol. Hydrogen-bonding analysis reveals that a large fraction of ethanols is involved in hydrogen bonds with lipids. This in turn is intimately coupled to the ordering of hydrocarbon chains: we find that binding to an ethanol decreases the order of the chains. We have also determined the dependence of lipid-chain ordering on ethanol concentration and found that to be nonmonotonous. Overall, we find good agreement with NMR and micropipette studies.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2005

Lateral pressure profiles in cholesterol-DPPC bilayers.

By means of atomistic molecular dynamics simulations, we study cholesterol-DPPC (dipalmitoyl phosphatidylcholine) bilayers of different composition, from pure DPPC bilayers to a 1:1 mixture of DPPC and cholesterol. The lateral pressure profiles through the bilayers are computed and separated into contributions from the different components. We find that the pressure inside the bilayer changes qualitatively for cholesterol concentrations of about 20% or higher. The pressure profile in the inside of the bilayer then turns from a rather flat shape into an alternating sequence of regions with large positive and negative lateral pressure. The changes in the lateral pressure profile are so characteristic that specific interaction between cholesterol and molecules such as membrane proteins mediated solely via the lateral pressure profile might become possible.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2005

Response to comment by Almeida et al.: free area theories for lipid bilayers--predictive or not?

Free area theories for lateral diffusion in lipid bilayers are reviewed and discussed. It has been suggested by Almeida et al. that free area theories yield quantitative predictions for lateral diffusion coefficients of lipids. We investigate the plausibility of this suggestion by first sketching what is to be expected of a quantitative theory with predictive power, and subsequently examining whether existing free area theories comply with these expectations. Our conclusion is that current free area theories for lipid bilayers are not quantitative theories with predictive power. They involve a number of adjustable parameters, all of which are not estimated independently, but derived from fitting the theory to the very data whose behavior the theory is supposed to predict. Further, the interpretation and behavior of some of the parameters are ambiguous. The best example is the so-called activation barrier, whose qualitative behavior with the cholesterol concentration in a DMPC bilayer varies depending on the experimental method used to generate the input data and the exact assumptions made to formulate the theory. Independent determination of the activation barrier from numerical simulations or experiments appears to be very difficult.

Animals↗

PubMed2004

Impact of cholesterol on voids in phospholipid membranes.

Free volume pockets or voids are important to many biological processes in cell membranes. Free volume fluctuations are a prerequisite for diffusion of lipids and other macromolecules in lipid bilayers. Permeation of small solutes across a membrane, as well as diffusion of solutes in the membrane interior are further examples of phenomena where voids and their properties play a central role. Cholesterol has been suggested to change the structure and function of membranes by altering their free volume properties. We study the effect of cholesterol on the properties of voids in dipalmitoylphosphatidylcholine (DPPC) bilayers by means of atomistic molecular dynamics simulations. We find that an increasing cholesterol concentration reduces the total amount of free volume in a bilayer. The effect of cholesterol on individual voids is most prominent in the region where the steroid ring structures of cholesterol molecules are located. Here a growing cholesterol content reduces the number of voids, completely removing voids of the size of a cholesterol molecule. The voids also become more elongated. The broad orientational distribution of voids observed in pure DPPC is, with a 30% molar concentration of cholesterol, replaced by a distribution where orientation along the bilayer normal is favored. Our results suggest that instead of being uniformly distributed to the whole bilayer, these effects are localized to the close vicinity of cholesterol molecules.

Algorithms↗

PubMed2004

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 pointlike 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 speedup 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 coarse-grained model, and discuss the general validity and applicability of the present approach.

Journal Article↗

PubMed2004

Systematic comparison of force fields for microscopic simulations of NaCl in aqueous solutions: diffusion, free energy of hydration, and structural properties.

In this article we compare different force fields that are widely used (Gromacs, Charmm-22/x-Plor, Charmm-27, Amber-1999, OPLS-AA) in biophysical simulations containing aqueous NaCl. We show that the uncertainties of the microscopic parameters of, in particular, sodium, and, to a lesser extent, chloride, translate into large differences in the computed radial-distribution functions. This uncertainty reflect the incomplete experimental knowledge of the structural properties of ionic aqueous solutions at finite molarity. We discuss possible implications on the computation of potential of mean force and effective potentials.

Journal Article↗

PubMed2004

Cationic DMPC/DMTAP lipid bilayers: molecular dynamics study.

Cationic lipid membranes are known to form compact complexes with DNA and to be effective as gene delivery agents both in vitro and in vivo. Here we employ molecular dynamics simulations for a detailed atomistic study of lipid bilayers consisting of a mixture of cationic dimyristoyltrimethylammonium propane (DMTAP) and zwitterionic dimyristoylphosphatidylcholine (DMPC). Our main objective is to examine how the composition of the DMPC/DMTAP bilayers affects their structural and electrostatic properties in the liquid-crystalline phase. By varying the mole fraction of DMTAP, we have found that the area per lipid has a pronounced nonmonotonic dependence on the DMTAP concentration, with a minimum around the point of equimolar DMPC/DMTAP mixture. We show that this behavior has an electrostatic origin and is driven by the interplay between positively charged TAP headgroups and the zwitterionic phosphatidylcholine (PC) heads. This interplay leads to considerable reorientation of PC headgroups for an increasing DMTAP concentration, and gives rise to major changes in the electrostatic properties of the lipid bilayer, including a significant increase of total dipole potential across the bilayer and prominent changes in the ordering of water in the vicinity of the membrane. Moreover, chloride counterions are bound mostly to PC nitrogens implying stronger screening of PC heads by Cl ions compared to TAP headgroups. The implications of these findings are briefly discussed.

Computer Simulation↗

PubMed2004

Lessons of slicing membranes: interplay of packing, free area, and lateral diffusion in phospholipid/cholesterol bilayers.

We employ 100-ns molecular dynamics simulations to study the influence of cholesterol on structural and dynamic properties of dipalmitoylphosphatidylcholine bilayers in the fluid phase. The effects of the cholesterol content on the bilayer structure are considered by varying the cholesterol concentration between 0 and 50%. We concentrate on the free area in the membrane and investigate quantities that are likely to be affected by changes in the free area and free volume properties. It is found that cholesterol has a strong impact on the free area properties of the bilayer. The changes in the amount of free area are shown to be intimately related to alterations in molecular packing, ordering of phospholipid tails, and behavior of compressibility moduli. Also the behavior of the lateral diffusion of both dipalmitoylphosphatidylcholine and cholesterol molecules with an increasing amount of cholesterol can in part be understood in terms of free area. Summarizing, our results highlight the central role of free area in comprehending the structural and dynamic properties of membranes containing cholesterol.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2003

Influence of spatial correlations on the lasing threshold of random lasers.

The lasing threshold of a random laser is computed numerically from a generic model. It is shown that spatial correlations of the disorder in the medium (i.e., dielectric constant) lead to an increase of the decay rates of the eigenmodes and of the lasing threshold. This is in conflict with predictions that such correlations should lower the threshold. While all results are derived for photonic systems, the computed decay rate distributions also apply to electronic systems.

Journal Article↗

PubMed2003

Stability of charge inversion, Thomson problem, and application to electrophoresis.

We analyze charge inversion in colloidal systems at zero temperature using stability concepts, and connect this to the classical Thomson problem of arranging electrons on sphere. We show that for a finite microion charge, the globally stable, lowest-energy state of the complex formed by the colloid and the oppositely charged microions is always overcharged. This effect disappears in the continuous limit. Additionally, a layer of at least twice as many microions as required for charge neutrality is always locally stable. In an applied external electric field the stability of the microion cloud is reduced. Finally, this approach is applied to a system of two colloids at low but finite temperature.

Journal Article↗