Molecular dynamics simulations have suggested that the formation of pores in the lipid bilayer occurs when water molecules align at the waterbilayer interface and are driven through the. By molecular dynamics simulations, biochemical and biophysical research communications on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Molecular dynamics simulations of lipid membrane electroporation article pdf available in journal of membrane biology 2459. Recently, molecular dynamics md simulations have been used to elucidate the molecular mechanisms leading to pore formation in simple lipid bilayers by both the application of an external electric field610 and the effects of dmso. As a result, membrane penetration and translocation of medium length oligoarginines becomes facilitated in comparison to single arginine and very long polyarginines, as well as to lysine containing peptides. Molecular dynamics simulation introduction electroporation is a process in which lipid membranes, the cell envelopes, are permeabilized when subjected to high electric. A novel engineered membrane to measure electroporation. Computer simulations of complexmembrane proteins such as potassium channels and atpbinding cassette transporters can give detailed information about the atomistic dynamics that forms the basis of ion transport, selectivity,conformational change, and the molecular. In the past decades, the diffusion of water in the nafion membrane was studied with molecular dynamics md simulation by many investigators, but the interfacial transport received little attention. Aggregation of oligoarginines at phospholipid membranes.
Membrane electroporation and electropermeabilization. Here i investigate the mechanism of pore formation by direct molecular dynamics simulations of phospholipid bilayers of a size of 256 and of more than 2000 lipids as well as simulations. Molecular dynamics simulations calculate the motion of the atoms in a molecular assembly using newtonian dynamics to determine the net force and acceleration experienced by each atom. Molecular dynamics simulation of membrane channels emad tajkhorshid beckman institute, uiuc summer school on theoretical and computational biophysics june 2004, university of western australia part i. Wetting characteristics of a phospholipid membrane using. Oct 04, 2011 atomistic and coarsegrained molecular dynamics simulations of membrane proteins. In this seminar, i will give an overview of the basic principles behind antimicrobial peptides and also look at the importance of membrane potentials in bacteria. An idealized molecularlevel scheme top and an atomiclevel molecular dynamics simulation bottom of electroporation with the electric. For example, one might apply artificial forces to pull a drug molecule off a protein, or push the simulation away from states it has already visited. Abstract electroporation relates to the cascade of events that follows the application of high electric. The pores can form without an external electric field acting on the membrane, but they are inherently unstable.
Stochastic diffusion of calcium ions through a nanopore in. We then present insights from molecularlevel modeling, particularly atomistic simulations that enhance. Henao1 1cell physiology group, electrophysiological models and electroporation. Pdf molecular dynamics simulations of the lipid bilayer. In very recent investigations, several key aspects of the electropermeabilization process were revealed from multi. The influences it shows that whether the electroporation can happen depends on the waveform of the applied terahertz electric field when the magnitude is not large enough. Each of these methods is effective in certain specific cases31. Ebtt workshop 2017 molecular dynamics simulations of membrane electroporation 2 which are sufficient to produce a transient trans membrane potential and an electrical field across the membrane of the order of 108 vm.
Membrane electroporation is the method to directly transfer bioactive substances such as drugs and genes into living cells, as well as preceding electrofusion. Formation of aqueous pores in the lipid bilayer is now a widely recognized mechanism, but evidence is growing that changes to individual membrane lipids and proteins also contribute, substantiating the need for terminological distinction between electroporation. Our simulations of electroporation show that the s. Kindt department of chemistry, emory university, atlanta, georgia 30322 abstract phospholipid bilayers have been intensively studied by molecular dynamics md simulation in recent years. Molecular dynamics simulations of stabilized pores by constant. Lipid pores with longer lifetimes are observed experimentally and in simulations when a low membrane. Methods the simulation method for studying membrane based separations used here has been described in detail previously 1117. Pef treatment, was reported for excitable biological cells in 1958 1, for nonexcitable cells in 1967 2, for lipid vesicles in 1972 3, and for planar lipid bilayers. Effects of dimethyl sulfoxide on lipid membrane electroporation. Conformational dynamics and membrane interactions of the e. Molecular simulationmembrane permeability wikibooks, open. Molecular dynamics simulations of membrane electroporation c3. The molecular basis of electroporation bmc biochemistry.
An idealized molecular level scheme top and an atomiclevel molecular dynamics simulation. Kinetics, statistics, and energetics of lipid membrane. Ultrafast electroporation of giant unilamellar vesicles experimental. Molecular dynamics simulations of lipid membrane electroporation. Electroporation of archaeal lipid membranes using md simulations. Lightning triggered electroporation and electrofusion as. Steered molecular dynamics is a nonequilibrium method by nature a wide variety of events that are inaccessible to conventional molecular dynamics simulations can be probed. Pdf molecular dynamics simulations of lipid membrane. Abstract we present results of molecular dynamics simulations of lipid bilayers under a high transverse electrical. Aug 16, 2017 molecular dynamics simulations of heterogeneous cell membranes in response to uniaxial membrane stretches at high loading rates skip to main content thank you for visiting.
Molecular dynamics md simulations were used to investigate the electroporation of archaeal lipid bilayers when subjected to high. Conformational dynamics within the nucleosome and chromatin structure play a key role in this. Molecular dynamics simulations of heterogeneous cell. Numerical study of the electroporation pulse shape effect. Terahertz electric fieldinduced membrane electroporation. Proceedings of the asme 2010 international mechanical engineering congress and exposition. The function of membranes and membrane proteins are determined by their structure, and the central focus of this thesis is the use of computational molecular dynamics simulations to study experimentally inaccessible details of membrane structure. This protocol combines hydrogendeuterium exchange mass spectrometry hdxms of membrane proteins in nanodiscs with molecular dynamics md simulations to identify lipidprotein.
Modeling and molecular dynamics of membrane proteins. Molecular dynamics simulation of water permeation through the. Here i investigate the mechanism of pore formation by direct molecular dynamics simulations of phospholipid bilayers of a size of 256 and of more than 2000 lipids as well as simulations of simpler interface systems with applied electric fields of different strengths. Molecular dynamics simulations have suggested that the formation of pores in the lipid bilayer occurs when water molecules align at the waterbilayer interface and are driven through the hydrophobic bilayer core by local electric field gradients 14, 71, 190,191. However, our coarsegrained molecular dynamics simulation results showed that membrane tension can restrain polyarginine translocation across the asymmetric membrane and that this effect increases.
Despite a wide range of applications, little is known about the electroporation threshold, which varies with membrane lipid composition. Molecular dynamics simulation of membrane channels brief introduction to membrane and a few examples of membrane channels aquaporin water channels how to model membrane proteins in membrane how to analyze the data. Stochastic diffusion of calcium ions through a nanopore in the cell membrane created by electroporation v. Several systems are studied, namely 1, a bare bilayer, 2, a bilayer containing a peptide nanotube channel, and 3, a system with a peripheral dna double strand. Tarek also used an allatomic molecular dynamics simulation to study the electroporation process 9, and his simulations showed that under an electric field, water molecules on each side of the. Molecular dynamics simulations of membrane electroporation. Mar 11, 2005 to date, the molecular processes involved in membrane electroporation are still poorly known.
On the electroporation thresholds of lipid bilayers. The estimated critical voltages for membrane electroporation are compared with the classical crowley prediction and recent molecular dynamics md simulations. Aug 15, 2008 in a recent molecular dynamics simulation study of a bilayer consisting of 2300 lipids in an external electric field of e 0. Enhancement of pore formation by electric fieldselectroporation exposure of biological membranes to a sufficiently high. Computer simulations of transport through membranes. After a certain degree of damage to the cell membranes by electroporation, the leakage of intracellular contents is too severe or the resealing of the cellular membrane is too slow, leaving healthy andor cancerous cells irreversibly damaged. We first describe the methods devised to perform in silico experiments of membranes subject to nanosecond, megavoltpermeter pulsed electric fields and of membranes subject to charge imbalance, mimicking therefore the application of lowvoltage, longduration pulses. Recent microsecondscale atomistic md simulations of mul.
Molecular dynamics simulation michel cuendet embl 2008 14. Electroporation is a process in which brief electrical pulses create transient pores in the plasma membrane that allow nucleic acids to enter the cellular cytoplasm. University of groningen permeation process of small molecules. This article reports on the progress made so far using such simulations to model membranelipid bilayerelectroporation. Here, we provide information on the history, mechanism, and optimization of electroporation. The function of membranes and membrane proteins are determined by their structure, and the central focus of this thesis is the use of computational molecular dynamics simulations to study experimentally inaccessible details of membrane. The aim of our study is to bring about a detailed molecular level picture of the phenomena,usingmolecular dynamics md simulations. Electroporation studied by molecular dynamics simulations rainer a. Report accelerated molecular dynamics simulations of ligand binding to a muscarinic gproteincoupled receptor kalli kappel1, yinglong miao2 and j. To date, the molecular processes involved in membrane electroporation are still poorly known.
Accelerated molecular dynamics simulations of ligand. Molecular dynamics md simulations of lipid membranes have come of age. Electroporation is a common method to introduce foreign molecules into cells, but its molecular basis is poorly understood. As a consequence, md simulations of electroporation model the. In the simulation, a 1palmitoyl 2oleoyl phosphatidylcholine popc bilayer. A variety of peptides induce pores in biological membranes. Jan 14, 2011 read effects of deformability and thermal motion of lipid membrane on electroporation. Second, we observe a strong tendency of adsorbed arginine but not lysine containing. Molecular dynamics simulation of reversible electroporation with. The mechanisms of poration for the two membranes have subtle differences.
Pdf the permeability of cell membranes can be transiently increased following the. The influences of the waveform and frequency of the applied terahertz electric field on the electroporation and the unique features of the process of the electroporation. The aim of our study is to bring about a detailed molecular level picture of the phenomena, using molecular dynamics md simulations. In this paper, the membrane electroporation induced by the terahertz electric field is simulated by means of the molecular dynamics method. In all systems, the applied transmembrane electric fields 0. This process is believed to involve 1 charging of the membrane. The method of molecular dynamics simulation is considered a powerful tool for elucidating the electroporation process. May 30, 2012 the permeability of cell membranes can be transiently increased following the application of external electric fields. Molecular dynamics simulations of the interactions of. Electroporation studied by molecular dynamics simulations. Pdf on the electroporation thresholds of lipid bilayers. Molecular dynamics simulations, timedependent fluorescence shift, and biomimetic colorimetric assays. We present results of molecular dynamics simulations of lipid bilayers under a high transverse electrical field aimed at investigating their electroporation.
Each atom i at position r i, is treated as a point with a mass m. This effect, generally referred to as membrane electroporation or by some authors as electropermeabilization and in food processing as. Although the allatom model can yield atomiclevel information about the process, the computational demand limits the simulation. Electroporation is a technique that causes the permeability of a biological membrane to increase in response to an applied. Ultrafast electroporation of giant unilamellar vesicles.
Antimicrobial peptide induced electroporation of lipid. Wetting characteristics of a phospholipid membrane using molecular dynamics simulation. Although much information on the microscopic mechanism has been obtained both from experiment and simulation. Permeation process of small molecules across lipid membranes studied by molecular dynamics simulations siewert j. Jun 19, 20 electroporation relates to the cascade of events that follows the application of high electric fields and that leads to cell membrane permeabilization. Kinetics, statistics, and energetics of lipid membrane electroporation. Molecular dynamics simulations of membranes and membrane. To address this, we have performed molecular dynamics simulations of two bacterial membranes. We have retained the chemical complexity of the membranes by considering the details of their lipidic components.
Previous molecular dynamics simulations of electroporation were based on allatom models. Hydrogen atoms on the lipid tails are omitted for clarity. After the discovery of membranereversible electroporation decades ago, the procedure has been used extensively in biology, biotechnology. Effects of deformability and thermal motion of lipid membrane. We therefore conclude that this model can be used to predict the effects of arbitrarily shaped electroporation pulses on cell membrane conductivity and molecular transport across the cell membrane. Berendsen department of biophysical chemistry, university of groningen, nijenborgh 4, 9747 ag groningen, the netherlands received. This page will automatically redirect to the new ads interface at that point. The computational biology group focuses on the structure, dynamics, and function of biological membrane mimics, including e. Theoretical approaches such as molecular modeling provide a significant insight into the processes affecting, at the molecular level, the integrity of lipid cell membranes when these are subject to voltage gradients under similar conditions as those used in experiments. Structural model of the migm bcell receptor transmembrane domain from selfassociation molecular dynamics simulations.