Simulations of the Morphological Evolution of Lipid Bilayer Membranes Using a Phase-Field Method

Phase-Field Modeling and Simulations of Lipid Membranes Coupling Composition with Membrane Mechanical Properties

In the present study, we propose a method for preparing stable free-standing bilayer lipid membranes (BLMs). The BLMs were prepared in a microfabricated aperture with a smoothly tapered edge, which was prepared in a nanometer-thick Si(3)N(4) septum by the wet etching method. Owing to this structure, the stress on lipid bilayers at the contact with the septum was minimized, leading to remarkable membrane stability. The BLMs were not broken by applying a constant voltage of +/-1 V. The membrane lifetime was 15-45 h with and without an incorporated gramicidin channel. Gramicidin single-channel currents were recorded from the same BLM preparation when the aqueous solutions surrounding the BLM were repeatedly exchanged, demonstrating the tolerance of the present BLM to repetitive solution exchanges. Such stable membranes enable analysis of channel functions under various solution conditions from the same BLM, which will open up a variety of applications including a high throughput drug screening for ion channels.

Porous polyoxometalate nanocapsules of Keplerate type are known to exhibit the functionality of biological ion channels; however, their use as an artificial ion channel is tempered by the high negative charge of the capsules, which renders their spontaneous incorporation into a lipid bilayer membrane unlikely. In this Letter we report coarse-grained molecular dynamics simulations that demonstrate a route for embedding negatively charged nanocapsules into lipid bilayer membranes via self-assembly. A homogeneous mixture of water, cationic detergent, and phospholipid was observed to spontaneously self-assemble around the nanocapsule into a layered, liposome-like structure, where the nanocapsule was enveloped by a layer of cationic detergent followed by a layer of phospholipid. Fusion of such a layered liposome with a lipid bilayer membrane was observed to embed the nanocapsule into the lipid bilayer. The resulting assembly was found to remain stable even after the surface of the capsule was exposed to electrolyte. In the latter conformation, water was observed to flow into and out of the capsule as Na(+) cations entered, suggesting that a polyoxometalate nanocapsule can form a functional synthetic ion channel in a lipid bilayer membrane.

We have applied a combined fluorescence microscopy and single-ion-channel electric current recording approach, correlating with molecular dynamics (MD) simulations, to study the mechanism of voltage-sensor domain translocation across a lipid bilayer. We use the colicin Ia ion channel as a model system, and our experimental and simulation results show the following: (1) The open-close activity of an activated colicin Ia is not necessarily sensitive to the amplitude of the applied cross-membrane voltage when the cross-membrane voltage is around the resting potential of excitable membranes; and (2) there is a significant probability that the activation of colicin Ia occurs by forming a transient and fluctuating water pore of ∼15 Å diameter in the lipid bilayer membrane. The location of the water-pore formation is nonrandom and highly specific, right at the insertion site of colicin Ia charged residues in the lipid bilayer membrane, and the formation is intrinsically associated with the polypeptide conformational fluctuations and solvation dynamics. Our results suggest an interesting mechanistic pathway for voltage-sensitive ion channel activation, and specifically for translocation of charged polypeptide chains across the lipid membrane under a transmembrane electric field: the charged polypeptide domain facilitates the formation of hydrophilic water pore in the membrane and diffuses through the hydrophilic pathway across the membrane; i.e., the charged polypeptide chain can cross a lipid membrane without entering into the hydrophobic core of the lipid membrane but entirely through the aqueous and hydrophilic environment to achieve a cross-membrane translocation. This mechanism sheds light on the intensive and fundamental debate on how a hydrophilic and charged peptide domain diffuses across the biologically inaccessible high-energy barrier of the hydrophobic core of a lipid bilayer: The peptide domain does not need to cross the hydrophobic core to move across a lipid bilayer.

Cellular membranes mediate vital cellular processes by being subject to curvature and transmembrane electrical potentials. Here we build upon the existing theory for flexoelectricity in liquid crystals to quantify the coupling between lipid bilayer curvature and membrane potentials. Using molecular dynamics simulations, we show that headgroup dipole moments, the lateral pressure profile across the bilayer, and spontaneous curvature all systematically change with increasing membrane potentials. In particular, there is a linear dependence between the bending moment (the product of bending rigidity and spontaneous curvature) and the applied membrane potentials. We show that biologically relevant membrane potentials can induce biologically relevant curvatures corresponding to radii of around 500 nm. The implications of flexoelectricity in lipid bilayers are thus likely to be of considerable consequence both in biology and in model lipid bilayer systems.

The lipid bilayer membrane is a major component of cells and intracellular membranes in vivo, and plays an indispensable role in organisms. Currently in the medical field, lipid bilayer membranes are used as devices for targeted delivery of proteins, nucleic acids and drugs in the treatment of a variety of diseases. Based on coarse-grained molecular dynamics (CGMD), this paper studies the modeling method of the lipid bilayer with water as solvent in the Martini force field. The coarse-grained lipid bilayer membrane model can expand the time scale and improves the computational efficiency of molecular dynamics (MD) simulation. The self-assembly process of DPPC bilayer lipid membrane is simulated in Martini force field and the radial distribution function (RDF) is also analyzed. In addition, this paper studies the molecular dynamics of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid bilayer membrane electroporation under Martini force field, which provides a theoretical reference for the application of coarse-grained molecular dynamics in biomedical and other related fields.

Formation of membrane necks is crucial for fission and fusion in lipid bilayers. In this work, we seek to answer the following fundamental question: what is the relationship between protein-induced spontaneous mean curvature and the Gaussian curvature at a membrane neck? Using an augmented Helfrich model for lipid bilayers to include membrane-protein interaction, we solve the shape equation on catenoids to find the field of spontaneous curvature that satisfies mechanical equilibrium of membrane necks. In this case, the shape equation reduces to a variable coefficient Helmholtz equation for spontaneous curvature, where the source term is proportional to the Gaussian curvature. We show how this latter quantity is responsible for non-uniform distribution of spontaneous curvature in minimal surfaces. We then explore the energetics of catenoids with different spontaneous curvature boundary conditions and geometric asymmetries to show how heterogeneities in spontaneous curvature distribution can couple with Gaussian curvature to result in membrane necks of different geometries.

Effect of acetylsalicylic acid on the current–voltage characteristics of planar lipid membranes

Evaluation of a glassy carbon electrode modified by a bilayer lipid membrane with incorporated DNA

Planar bilayer lipid membranes (BLMs) are widely used as models for cell membranes in various applications, including drug discovery and biosensors. However, the nanometer‐thick bilayer structure, assembled through hydrophobic interactions of amphiphilic lipid molecules, makes such BLM systems mechanically and electrically unstable. In this study, we developed a device to reform BLMs using a microair bubble. The device consists of a double well divided by a separator with a microaperture, where a BLM was formed by infusing a lipid‐dispersed solvent and an aqueous droplet into each well in series. When the BLM ruptured, a microair bubble was injected from the bottom of the well to split the merged aqueous droplet at the microaperture, which resulted in the reformation of two lipid monolayers on the split droplets. By bringing the two droplets into contact, a new BLM was formed. An angled step design was introduced in the BLM device to guide the bubble and ensure the splitting of the merged droplet. We also elucidated the optimal bubble inflow rate for the reproducible BLM reformation. Using a 4‐channel parallel device, we demonstrated the individual and repeatable reformation of BLMs. Our approach will aid the development of automated and arrayed BLM systems.

Ion transport from one aqueous phase (W1) to another (W2) across a planar bilayer lipid membrane (BLM) in the presence of inhalation anesthetics was electrochemically investigated. In the absence of inhalation anesthetics in the BLM system, no ion transport current flowed between W1 and W2 across the BLM. When inhalation anesthetics such as halothane, chloroform, diethyl ether and trichloroethylene were added to the two aqueous phases or the BLM, the ion transport current quite clearly appeared. When the ratio of the concentration of KCl or NaCl in W1 to that in W2 was varied, the zero current potential across the BLM was shifted. By considering the magnitude of the potential shift, we concluded that the ion transport current can be predominantly ascribed to the transport of Cl(-) across the BLM. Since the dielectric constants of these anesthetics are larger than that of the inner hydrophobic domain of the BLM, the concentration of hydrophilic electrolyte ions in the BLM increases with the increase in the dielectric constant of the inner hydrophobic domain caused by addition of these anesthetics. These situations lead to an increase in the ion permeability coefficient.

Vesicles are membrane-bound structures commonly known for their roles in cellular transport and the shape of a vesicle is determined by its surrounding membrane (lipid bilayer). When the membrane is composed of different lipids, it is natural for the lipids of similar molecular structure to migrate towards one another (via spinodal decomposition), creating a multi-phase vesicle. In this article, we consider a two-phase vesicle model which is driven by nature's propensity to maintain a minimal state of elastic energy. The model assumes a continuum limit, thereby treating the membrane as a closed three-dimensional surface. The main purpose of this study is to reveal the complexity of the Helfrich two-phase vesicle model with non-zero spontaneous curvature and provide further evidence to support the relevance of spontaneous curvature as a modelling parameter.In this paper, we illustrate the complexity of the Helfrich two-phase model by providing multiple examples of undocumented solutions and energy hysteresis. We also investigate the influence of spontaneous curvature on morphological effects and membrane phenomena such as budding and fusion.

Formation of self-assembled lipid bilayers on solid substrates

The electrostriction, surface potential and capacitance relaxation of bilayer lipid membranes induced by tetracaine

Introducing multiphase structures into benzoxazine (BOZ)/epoxy resins (ER) blends via reaction-induced phase separation has proved to be promising strategy for improving their toughness. However, due to the limited contrast between two phases, little information is known about the phase morphological evolutions, a fundamental but vital issue to rational design and preparation of blends with different phase morphologies in a controllable manner. Here we addressed this problem by amplifying the difference of polymerization activity (PA) between BOZ and ER by synthesizing a low reactive phenol-3,3-diethyl-4,4′-diaminodiphenyl methane based benzoxazine (MOEA-BOZ) monomer. Results indicated that the PA of ER was higher than that of BOZ. The use of less reactive MOEA-BOZs significantly enlarged their PA difference with ER, and thus increased the extent of phase separation and improved the phase contrast. Phase morphologies varied with the content of ER. As for the phase morphological evolution, a rapid phase separation could occur in the initial homogeneous blends with the polymerization of ER, and the phase morphology gradually evolved with the increase in ER conversion until the ER was used up. The polymerization of ER is not only the driving-force for the phase separation, but also the main factor influencing the phase morphologies.