Bubbles in water under stretch-induced cavitation.

When a finite sample of water experiences tension, it may develop voids (bubbles). We present here a result for the work (Helmholtz free energy change) that needs to be done for the creation of a bubble in fixed volume of water under tension and show that this result depends on the general form of stress-strain relationship. We observe that it is very important to include the curvature-dependent surface tension into consideration in order to explain bubble stability. The analytical result we obtained for the free energy allows us to make prediction for the values of critical and stable radii of the bubbles. We also performed simulations on the TIP4P/2005 water model and observed creation of bubbles in water under stretch. Combining analytical results obtained from our thermodynamic description with the results from computer simulations allowed us to determine the two parameters that describe the curvature-dependent surface tension and also to find the values of critical and stable bubble radii. We also determined the values of critical bubble radii by using mean first-passage time calculations.

A comparative computational study of coarse-grained and all-atom water models in shock Hugoniot states.

We performed molecular dynamics simulations to study how well some of the water models used in simulations describe shocked states. Water in our simulations was described using three different models. One was an often-used all-atom TIP4P/2005 model, while the other two were coarse-grained models used with the MARTINI force field: non-polarizable and polarizable MARTINI water. The all-atom model provided results in good agreement with Hugoniot curves (for data on pressure versus specific volume or, equivalently, on shock wave velocity versus "piston" velocity) describing shocked states in the whole range of pressures (up to 11 GPa) under study. If simulations of shocked states of water using coarse-grained models were performed for short time periods, we observed that data obtained for shocked states at low pressure were fairly accurate compared to experimental Hugoniot curves. Polarizable MARTINI water still provided a good description of Hugoniot curves for pressures up to 11 GPa, while the results for the non-polarizable MARTINI water substantially deviated from the Hugoniot curves. We also calculated the temperature of the Hugoniot states and observed that for TIP4P/2005 water, they were consistent with those from theoretical calculations, while both coarse-grained models predicted much higher temperatures. These high temperatures for MARTINI water can be explained by the loss of degrees of freedom due to coarse-graining procedure.

Shock Wave-Induced Damage of a Protein by Void Collapse.

In this study, we report on a series of molecular dynamics simulations that were used to examine the effects of shock waves on a membrane-bound ion channel. A planar shock wave was found to compress the ion channel upon impact, but the protein geometry resembles the crystal structure as soon as the solvent density begins to dissipate. When a void was placed in close proximity to the membrane, the shock wave proved to be more destructive to the protein due to formation of a nanojet that results from the asymmetric collapse of the void. The nanojet was able to cause significant structural changes to the protein even at low piston velocities that are not able to directly cause poration of the membrane.

Nanobubbles, cavitation, shock waves and traumatic brain injury.

Collapse of bubbles, microscopic or nanoscopic, due to their interaction with the impinging pressure wave produces a jet of particles moving in the direction of the wave. If there is a surface nearby, the high-speed jet particles hit it, and as a result damage to the surface is produced. This cavitation effect is well known and intensely studied in case of microscopic sized bubbles. It can be quite damaging to materials, including biological tissues, but it can also be beneficial when controlled, like in case of sonoporation of biological membranes for the purpose of drug delivery. Here we consider recent simulation work performed to study collapse of nanobubbles exposed to shock waves, in order to understand the detailed mechanism of the cavitation induced damage to soft materials, such as biological membranes. We also discuss the connection of the cavitation effect with the traumatic brain injury caused by blasts. Specifically, we consider possible damage to model membranes containing lipid bilayers, bilayers with embedded ion channel proteins like the ones found in neural cells and also protein assemblies found in the tight junction of the blood brain barrier.

Communication: Modeling of concentration dependent water diffusivity in ionic solutions: Role of intermolecular charge transfer.

The translational diffusivity of water in solutions of alkali halide salts depends on the identity of ions, exhibiting dramatically different behavior even in solutions of similar salts of NaCl and KCl. The water diffusion coefficient decreases as the salt concentration increases in NaCl. Yet, in KCl solution, it slightly increases and remains above bulk value as salt concentration increases. Previous classical molecular dynamics simulations have failed to describe this important behavior even when polarizable models were used. Here, we show that inclusion of dynamical charge transfer among water molecules produces results in a quantitative agreement with experiments. Our results indicate that the concentration-dependent diffusivity reflects the importance of many-body effects among the water molecules in aqueous ionic solutions. Comparison with quantum mechanical calculations shows that a heterogeneous and extended distribution of charges on water molecules around the ions due to ion-water and also water-water charge transfer plays a very important role in controlling water diffusivity. Explicit inclusion of the charge transfer allows us to model accurately the difference in the concentration-dependent water diffusivity between Na(+) and K(+) ions in simulations, and it is likely to impact modeling of a wide range of systems for medical and technological applications.

Shock wave interaction with a phospholipid membrane: coarse-grained computer simulations.

We used MARTINI coarse-grained force field to study poration of a lipid bilayer by a shock wave induced nanobubble collapse. Different systems containing different sized nanobubbles that were exposed to shock waves propagating with different velocities were simulated. We observed creation of pores and damage to bilayers and also subsequent pore closing and the bilayer recovery after shock wave passed the bilayer. In all our systems where bilayers were damaged, they recovered; nevertheless we observed that a large amount of water crossed the pore that was temporarily created. We also observed that not every lipid molecule remained in the bilayer after recovery, some lipids moved out into water and created micelles.

Binding and reorientation of melittin in a POPC bilayer: computer simulations.

We performed, using an all-atom force field, molecular dynamics computer simulations to study the binding of melittin to the POPC bilayer and its subsequent reorientation in this bilayer. The binding process involves a simultaneous folding and adsorption of the peptide to the bilayer, followed by the creation of a "U shaped" conformation. The reorientation of melittin from the parallel to the perpendicular conformation requires charged residues to cross the hydrophobic core of the bilayer. This is accomplished by a creation of defects in the bilayer that are filled out with water. The defects are caused by peptide charged residues dragging the lipid headgroup atoms along with them, as they reorient. With increased concentration of melittin water defects form stable pores; this makes it easier for the peptide N-terminus to reorient. Our results complement experimental and computational observations of the melittin/lipid bilayer interaction.

Aqueous solutions at the interface with phospholipid bilayers.

In a sense, life is defined by membranes, because they delineate the barrier between the living cell and its surroundings. Membranes are also essential for regulating the machinery of life throughout many interfaces within the cell's interior. A large number of experimental, computational, and theoretical studies have demonstrated how the properties of water and ionic aqueous solutions change due to the vicinity of membranes and, in turn, how the properties of membranes depend on the presence of aqueous solutions. Consequently, understanding the character of aqueous solutions at their interface with biological membranes is critical to research progress on many fronts. The importance of incorporating a molecular-level description of water into the study of biomembrane surfaces was demonstrated by an examination of the interaction between phospholipid bilayers that can serve as model biological membranes. The results showed that, in addition to well-known forces, such as van der Waals and screened Coulomb, one has to consider a repulsion force due to the removal of water between surfaces. It was also known that physicochemical properties of biological membranes are strongly influenced by the specific character of the ions in the surrounding aqueous solutions because of the observation that different anions produce different effects on muscle twitch tension. In this Account, we describe the interaction of pure water, and also of aqueous ionic solutions, with model membranes. We show that a symbiosis of experimental and computational work over the past few years has resulted in substantial progress in the field. We now better understand the origin of the hydration force, the structural properties of water at the interface with phospholipid bilayers, and the influence of phospholipid headgroups on the dynamics of water. We also improved our knowledge of the ion-specific effect, which is observed at the interface of the phospholipid bilayer and aqueous solution, and its connection with the Hofmeister series. Nevertheless, despite substantial progress, many issues remain unresolved. Thus, for example, we still cannot satisfactorily explain the force of interaction between phospholipid bilayers immersed in aqueous solutions of NaI. Although we try to address many issues here, the scope of the discussion is limited and does not cover such important topics as the influence of ionic solutions on phases of bilayers, the influence of salts on the properties of Langmuir monolayers containing lipid molecules, or the influence of aqueous solutions on bilayers containing mixtures of lipids. We anticipate that the future application of more powerful experimental techniques, in combination with more advanced computational hardware, software, and theory, will produce molecular-level information about these important topics and, more broadly, will further illuminate our understanding of interfaces between aqueous solutions and biological membranes.

Influence of the arrangement and secondary structure of melittin peptides on the formation and stability of toroidal pores.

Melittin interactions with lipid bilayers and melittin formed pores are extensively studied to understand the mechanism of the toroidal pore formation. Early experimental studies suggested that melittin peptide molecules are anchored by their positively charged residues located next to the C-terminus to only one leaflet of the lipid bilayer (asymmetric arrangement). However, the recent non-linear spectroscopic experiment suggests a symmetric arrangement of the peptides with the C-terminus of the peptides anchored to both bilayers. Therefore, we present here a computational study that compares the effect of symmetric and asymmetric arrangements of melittin peptides in the toroidal pore formation. We also investigate the role of the peptide secondary structure during the pore formation. Two sets of the symmetric and asymmetric pores are prepared, one with a helical peptide from the crystal structure and the other set with a less helical peptide. We observe a stable toroidal pore being formed only in the system with a symmetric arrangement of the less helical peptides. Based on the simulation results we propose that the symmetric arrangement of the peptides might be more favorable than the asymmetric arrangement, and that the helical secondary structure is not a prerequisite for the formation of the toroidal pore.

Molecular dynamics simulation study of the water-mediated interaction between zwitterionic and charged surfaces.

We calculated the potential of mean force (PMF) for the interaction between a model zwitterionic bilayer and a model charged bilayer. To understand the role of water, we separated the PMF into two components: one due to direct interaction and the other due to water-mediated interaction. In our calculations, we observed that water-mediated interaction is attractive at larger distances and repulsive at shorter. The calculation of the entropic and enthalpic contributions to the solvent-mediated components of the PMF showed that attraction is entropically dominant, while repulsion is dominated by the enthalpy.

Restructuring of hydrophobic surfaces created by surfactant adsorption to mica surfaces.

Hydrophobic surfaces created by the adsorption of a monolayer of surfactants, such as CTAB or DODAB, to mica display long-range mutual attraction when placed in water. Initially, this attraction was considered to be due to hydrophobic interaction, but more careful measurements using AFM showed that the surfactant monolayer undergoes rearrangements to produce charged patches on the surface; therefore, the nature of the long-range interaction is due to the electrostatic interaction between patches. The monolayer rearrangement depends on the nature of the surfactant and its counterion. To study possible monolayer rearrangements in molecular detail, we performed detailed molecular dynamics computer simulations on systems containing a monolayer of surfactants RN(CH(3))(3)(+)Cl(-) (R indicates a saturated hydrocarbon chain) adsorbed on a mica surface and immersed in water. We observe that when chain R is 18 carbons long the monolayer rearranges into a micelle but it remains a monolayer when the chain contains 24 carbons.

Role of water in atomic resolution AFM in solutions.

We use computer modelling to investigate the mechanism of atomic-scale corrugation in frequency modulation atomic force microscopy imaging of inorganic surfaces in solution. Molecular dynamics simulations demonstrate that the forces acting on a model microscope tip result from the direct interaction between a tip and a surface, and forces entirely due to the water structure around both tip and surface. The observed force is a balance between largely repulsive potential energy changes as the tip approaches and the entropic gain when water is sterically prevented from occupying sites near the tip and surface. Only extremely sharp tips are likely to measure direct tip-surface interactions. An investigation into the dynamics of water confined between tip and surface shows that water diffusion can be slowed by at least two orders of magnitude compared to its rate in bulk solution.

Molecular dynamics simulation study of interaction between model rough hydrophobic surfaces.

We study some aspects of hydrophobic interaction between molecular rough and flexible model surfaces. The model we use in this work is based on a model we used previously (Eun, C.; Berkowitz, M. L. J. Phys. Chem. B 2009, 113, 13222-13228), when we studied the interaction between model patches of lipid membranes. Our original model consisted of two graphene plates with attached polar headgroups; the plates were immersed in a water bath. The interaction between such plates can be considered as an example of a hydrophilic interaction. In the present work, we modify our previous model by removing the charge from the zwitterionic headgroups. As a result of this procedure, the plate character changes: it becomes hydrophobic. By separating the total interaction (or potential of mean force, PMF) between plates into the direct and the water-mediated interactions, we observe that the latter changes from repulsive to attractive, clearly emphasizing the important role of water as a medium. We also investigate the effect of roughness and flexibility of the headgroups on the interaction between plates and observe that roughness enhances the character of the hydrophobic interaction. The presence of a dewetting transition in a confined space between charge-removed plates confirms that the interaction between plates is strongly hydrophobic. In addition, we notice that there is a shallow local minimum in the PMF in the case of the charge-removed plates. We find that this minimum is associated with the configurational changes that flexible headgroups undergo as the two plates are brought together.

Stretch-Induced Cavitation: How Critical Cavity Radius and Barrier Energy, Radius, and Energy of a Stable Cavity Depend on the Stretching Factor.

Characteristics of tension-induced cavitation, such as free energy at the barrier for cavitation, the size of the critical (barrier) cavity, the stable cavity size, and the free energy of the stable cavity, depend on the amount of tension (stretch) and the initial size of the sample. In this work, we study how the characteristics of the cavitation mentioned above scale with the amount of applied tension. We consider two models characterizing the properties of cavitating liquid: (a) a simple model with a linear tension-strain relation and neglect of curvature dependence of cavity surface tension and (b) a more realistic model with a nonlinear tension-strain relation and curvature-dependent surface tension. For both models, we find the relevant scaling relations when we stretch the initial volume of the liquid sample in the interval between 1% and 20% of the initial volume. Specific numerical tests are performed for the case of liquid water when the initial volume of the sample is a sphere with a radius of 100 nm.

Molecular Simulations of Aqueous Electrolytes: Role of Explicit Inclusion of Charge Transfer into Force Fields.

We describe here simulations of aqueous salt solutions that are performed using an explicit charge transfer force field. The emphasis of the discussion is on the calculation of a dynamical property of the solutions: self-diffusion of water. While force fields that are based on pairwise additive potentials or on potentials with explicit inclusion of polarization or with scaled charges can provide at best a qualitative agreement with experiments, force fields with explicit inclusion of charge transfer can produce quantitative agreement with experiment for NaCl and KCl solutions. We argue that a force field with explicit charge transfer contains new physics absent in the previously used force fields described in recent reviews of molecular simulations of aqueous electrolytes.

Detailed molecular dynamics simulations of model biological membranes containing cholesterol.

Detailed molecular dynamics simulations performed to study the nature of lipid raft domains that appear in model membranes are reviewed in this paper. The described simulations were performed on hydrated bilayers containing binary mixtures of cholesterol with phospholipids and also on ternary mixtures containing cholesterol, a phospholipid with a high main transition temperature T(m), and a phospholipid with a low transition temperature T(m). These simulations provide qualitative and semi-quantitative information about cholesterol-lipid interactions and also a testing ground for major assumptions made to explain the nature of lipid rafts in model membranes.

A molecular dynamics study of the early stages of amyloid-beta(1-42) oligomerization: the role of lipid membranes.

As research progresses toward understanding the role of the amyloid-beta (Abeta) peptide in Alzheimer's disease, certain aspects of the aggregation process for Abeta are still not clear. In particular, the accepted constitution of toxic aggregates in neurons has shifted toward small oligomers. However, the process of forming these oligomers in cells is also not full clear. Even more interestingly, it has been implied that cell membranes, and, in particular, anionic lipids within those membranes, play a key role in the progression of Abeta aggregation, but the exact nature of the Abeta-membrane interaction in this process is unknown. In this work, we use a thermodynamic cycle and umbrella sampling molecular dynamics to investigate dimerization of the 42-residue Abeta peptide on model zwitterionic dipalmitoylphosphatidylcholine (DPPC) or model anionic dioleoylphosphatidylserine (DOPS) bilayer surfaces. We determined that Abeta dimerization was strongly favored through interactions with the DOPS bilayer. Further, our calculations showed that the DOPS bilayer promoted strong protein-protein interactions within the Abeta dimer, whereas DPPC favored strong protein-lipid interactions. By promoting dimer formation and subsequent dimer release into the solvent, the DOPS bilayer acts as a catalyst in Abeta aggregation.

Damage to Polystyrene Polymer Film by Shock Wave Induced Bubble Collapse.

Metallic surfaces that are in contact with solutions are commonly used in numerous applications where these surfaces can be damaged by shock wave induced bubble collapse. Use of polymer films that coat such surfaces to prevent them from damage requires a better understanding of how much harm collapsing bubbles produce in the films. In this study, we report the results from coarse-grained molecular dynamics simulations to study the damage to polystyrene (PS) films coating a hard surface. The damage was caused by a collapsing nanobubble located in the proximity of the film and interacting with an impinging shock wave. This collapse produces a high-speed water jet that impacts the PS film with a greater force than the shock front and creates cavities/pits in the PS film. We observed that polymer molecules located in the jet vicinity undergo conformational extension in the direction perpendicular to the jet motion, while chain molecules in the rest of the film undergo compression. We also observed that damage to the film is sensitive to the strength of the shock wave.

Molecular model of a cell plasma membrane with an asymmetric multicomponent composition: water permeation and ion effects.

We present molecular dynamics simulations of a multicomponent, asymmetric bilayer in mixed aqueous solutions of sodium and potassium chloride. Because of the geometry of the system, there are two aqueous solution regions in our simulations: one mimics the intracellular region, and one mimics the extracellular region. Ion-specific effects are evident at the membrane/aqueous solution interface. Namely, at equal concentrations of sodium and potassium, sodium ions are more strongly adsorbed to carbonyl groups of the lipid headgroups. A significant concentration excess of potassium is needed for this ion to overwhelm the sodium abundance at the membrane. Ion-membrane interactions also lead to concentration-dependent and cation-specific behavior of the electrostatic potential in the intracellular region because of the negative charge on the inner leaflet. In addition, water permeation across the membrane was observed on a timescale of approximately 100 ns. This study represents a step toward the modeling of realistic biological membranes at physiological conditions in intracellular and extracellular environments.

Interaction between amyloid-beta (1-42) peptide and phospholipid bilayers: a molecular dynamics study.

The amyloid-beta (Abeta) peptide is a key aggregate species in Alzheimer's disease. Although important aspects of Abeta peptide aggregation are understood, the initial stage of aggregation from monomer to oligomer is still not clear. One potential mediator of this early aggregation process is interactions of Abeta with anionic cell membranes. We used unconstrained and umbrella sampling molecular dynamics simulations to investigate interactions between the 42-amino acid Abeta peptide and model bilayers of zwitterionic dipalmitoylphosphatidylcholine (DPPC) lipids and anionic dioleoylphosphatidylserine (DOPS) lipids. Using these methods, we determined that Abeta is attracted to the surface of DPPC and DOPS bilayers over the small length scales used in these simulations. We also found supporting evidence that the charge on both the bilayer surface and the peptide affects the free energy of binding of the peptide to the bilayer surface and the distribution of the peptide on the bilayer surface. Our work demonstrates that interactions between the Abeta peptide and lipid bilayer promotes a peptide distribution on the bilayer surface that is prone to peptide-peptide interactions, which can influence the propensity of Abeta to aggregate into higher-order structures.