Force among magnetic nanocylinders trapped in triangular arrays

We study the effect of the forces among magnetic nanocylinders trapped in a membrane such as those used to produce them. The interaction force between two parallel and identical magnetic nanocylinders is revisited to obtain expressions that can later be used to add them both in a discrete and a continuum approximation. At this point a particular geometry has to be assumed and we use a particular configuration reported in the literature, namely, a bundle of parallel magnetic cylinders trapped in a circular membrane. When a strong enough external magnetic field is imposed along the axis of the membrane (also along the axes of the cylinders) all magnetizations point along this direction and cylinders repel among themselves. In a first approximation we will consider a soft enough membrane so energy is mostly relaxed through a deformation of the membrane leaving the magnetization of the cylinders basically as it was in the absence of external field. Then we obtain the forces among these cylinders by two methods: one summing the contributions of a discrete number of objects and another one in which we consider a continuum distribution of them to reach larger systems. Numerical evaluation of these forces can reach 50 mdyn approximately. Such forces will act on the membrane at the positions of the magnetic cylinders; in the case of a circular silicon membrane of radius 1.0 mm the radial expansion of the membrane can be of the order of 1 nm. This effect could be larger for softer membranes. A discussion of experimental techniques to detect this phenomenon is also done followed by the proposal of a possible application.     

Diffusion Limitations and Translocation Barriers in Atomically Thin Biomimetic Pores

Ionic transport in nano- to sub-nano-scale pores is highly dependent on translocation barriers and potential wells. These features in the free-energy landscape are primarily the result of ion dehydration and electrostatic interactions. For pores in atomically thin membranes, such as graphene, other factors come into play. Ion dynamics both inside and outside the geometric volume of the pore can be critical in determining the transport properties of the channel due to several commensurate length scales, such as the effective membrane thickness, radii of the first and the second hydration layers, pore radius, and Debye length. In particular, for biomimetic pores, such as the graphene crown ether we examine here, there are regimes where transport is highly sensitive to the pore size due to the interplay of dehydration and interaction with pore charge. Picometer changes in the size, e.g., due to a minute strain, can lead to a large change in conductance. Outside of these regimes, the small pore size itself gives a large resistance, even when electrostatic factors and dehydration compensate each other to give a relatively flat—e.g., near barrierless—free energy landscape. The permeability, though, can still be large and ions will translocate rapidly after they arrive within the capture radius of the pore. This, in turn, leads to diffusion and drift effects dominating the conductance. The current thus plateaus and becomes effectively independent of pore-free energy characteristics. Measurement of this effect will give an estimate of the magnitude of kinetically limiting features, and experimentally constrain the local electromechanical conditions.     

Protein transfer to membranes upon shape deformation

Red blood cells, milk fat droplets, or liposomes all have interfaces consisting of lipid membranes. These particles show significant shape deformations as a result of flow. Here we show that these shape deformations can induce adsorption of proteins to the membrane. Red blood cell deformability is an important factor in several diseases involving obstructions of the microcirculatory system, and deformation induced protein adsorption will alter the rigidity of their membranes. Deformation induced protein transfer will also affect adsorption of cells onto implant surfaces, and the performance of liposome based controlled release systems. Quantitative models describing this phenomenon in biomaterials do not exist. Using a simple quantitative model, we provide new insight in this phenomenon. We present data that show convincingly that for cells or droplets with diameters upwards of a few micrometers, shape deformations induce adsorption of proteins at their interface even at moderate flow rates.     

Optical detection of pores in adipocyte membrane

Structures that can be interpreted as cytoplasm droplets leaking through the membrane are experimentally detected on the membranes of adipocytes using optical digital microscopy. The effect of an aqueous alcohol solution of brilliant green on the amount and sizes of structures is studied. It is demonstrated that the optical irradiation of the adipocytes that are sensitized with the aid of the brilliant green leads to an increase in the amount of structures (pores) after the irradiation. The experimental results confirm the existence of an earlier-proposed effect of photochemical action on the sensitized cells of adipose tissue that involves additional formation of pores in the membrane of the sensitized cell under selective optical irradiation. The proposed method for the detection of micropores in the membrane of adipose tissue based on the detection of the cytoplasm droplets leaking from the cell can be considered as a method for the optical detection of nanosized pores.     

Cytotoxic Killing and Immune Evasion by Repair

The interaction between the immune system and pathogens is a complex one, with pathogens constantly developing new ways of evading destruction by the immune system. The immune system's task is made even harder when the pathogen in question is an intra-cellular one (such as a virus or certain bacteria) and it is necessary to kill the infected host cell in order to eliminate the pathogen. This causes damage to the host, and such killing therefore needs to be carefully controlled, particularly in tissues with poor regenerative potential, or those involved in the immune response itself. Host cells therefore possess repair mechanisms which can counteract killing by immune cells. These in turn can be subverted by pathogens which up-regulate the resistance of infected cells to killing. In this paper, we explore the hypothesis that this repair process plays an important role in determining the efficacy of evasion and escape from immune control. We model a situation where cytotoxic T lymphocytes (CTL) and natural killer (NK) cells kill pathogen-infected and tumour cells by directed secretion of preformed granules containing perforin and granzymes. Resistance to such killing can be conferred by the expression of serine protease inhibitors (serpins). These are utilized by several virally infected and tumour cells, as well as playing a role in the protection of host bystander, immune and immuneprivileged cells. We build a simple stochastic model of cytotoxic killing, where serpins can neutralize granzymes stoichiometrically by forming an irreversible complex, and the survival of the cell is determined by the balance between serpin depletion and replenishment, which in its simplest form is equivalent to the well known shot noise process. We use existing analytical results for this process, and additional simulations to analyse the effects of repair on cytotoxic killing. We then extend the model to the case of a replicating target cell population, which gives a branching process coupled to shot noise. We show how the process of repair can have a major impact on the dynamics of pathogen evasion and escape of tumour cells from immune surveillance     

Phosphoinositide-binding interface proteins involved in shaping cell membranes

The mechanism by which cell and cell membrane shapes are created has long been a subject of great interest. Among the phosphoinositide-binding proteins, a group of proteins that can change the shape of membranes, in addition to the phosphoinositide-binding ability, has been found. These proteins, which contain membrane-deforming domains such as the BAR, EFC/F-BAR, and the IMD/I-BAR domains, led to inward-invaginated tubes or outward protrusions of the membrane, resulting in a variety of membrane shapes. Furthermore, these proteins not only bind to phosphoinositide, but also to the N-WASP/WAVE complex and the actin polymerization machinery, which generates a driving force to shape the membranes.     

Real‐Time Detection of Nanoparticles Interaction with Lipid Membranes Using an Integrated Acoustical and Electrical Multimode Biosensor

Understanding interactions of nanoparticles with biomembranes is critical in nanomedicine and nanobiotechnology. The underlying mechanisms still remain unclear due to the fact that there are no reliable tools to follow such complex processes. In this work, the interactions between gold nanoparticles (AuNPs) and the supported lipid bilayer (SLB) are monitored in situ by a multimode biosensor integrating a quartz crystal microbalance with dissipation function (QCM‐D) and a field effect transistor (FET). Real‐time responses of frequency shift (Δf), dissipation (ΔD), and ion current (ΔI) are simultaneously recorded to provide complementary information for AuNPs translocation across the SLB. The combined mass loading, mechanical and electrical measurements reveal the dynamics of the particle–membrane interactions as well as the formation of transient pores or permanent defects in the membrane. AuNPs with different diameters, surface charge, and ligand properties are used to study their translocation behaviors, including adsorption on or desorption from the membrane surface, diffusion into or penetration through the lipid bilayer. This multimode sensing approach provides insights into the mechanism of the particle–membrane interactions and suggests a method of label‐free screening of nanomaterials' interaction with model membranes in a real‐time manner.     

Pore dynamics of osmotically stressed vesicles

We present a theory for pore dynamics of osmotically stressed vesicles. When a liposome with an internal concentration of solute is placed inside a solute-depleted medium, an osmotic flow of solvent through the lipid bilayer leads to swelling of vesicle and to increase in membrane surface tension. This can result in membrane rupture and opening of thermal pores. Depending on the internal concentration of solute and the size of the vesicle, pores can close rapidly or be long lived. We find that the life span of the long-lived pores scales non-trivially with the size of the liposome. Closure of the long-lived pore is followed by a rapid flicker-like opening and closing of short-lived pores. Our model is consistent with the observation of long-lived pores in red blood cell ghosts.     

Electrostatic and electrokinetic contributions to the elastic moduli of a driven membrane

We discuss the electrostatic contribution to the elastic moduli of a cell or artificial membrane placed in an electrolyte and driven by a DC electric field. The field drives ion currents across the membrane, through specific channels, pumps or natural pores. In steady state, charges accumulate in the Debye layers close to the membrane, modifying the membrane elastic moduli. We first study a model of a membrane of zero thickness, later generalizing this treatment to allow for a finite thickness and finite dielectric constant. Our results clarify and extend the results presented by D. Lacoste, M. Cosentino Lagomarsino, and J.F. Joanny (EPL 77, 18006 (2007)), by providing a physical explanation for a destabilizing term proportional to k _⊥ ³ in the fluctuation spectrum, which we relate to a nonlinear (E²) electrokinetic effect called induced-charge electro-osmosis (ICEO). Recent studies of ICEO have focused on electrodes and polarizable particles, where an applied bulk field is perturbed by capacitive charging of the double layer and drives the flow along the field axis toward surface protrusions; in contrast, we predict “reverse” ICEO flows around driven membranes, due to curvature-induced tangential fields within a nonequilibrium double layer, which hydrodynamically enhance protrusions. We also consider the effect of incorporating the dynamics of a spatially dependent concentration field for the ion channels.     

Optical methods for the study of dynamics in biological membrane models

Membranes are highly complex and heterogeneous interfaces that are the active partition between living cells and the outside world. Many biologically important processes occur at the membrane surface, such as transmembrane transport and signaling. Many of these processes depend on the subtle interactions between the different membrane constituents: lipids, proteins and water. At present, a large body of knowledge exists on the molecular composition and static structure of membranes. However, our understanding of the dynamics of membrane molecules has not yet reached the same level of sophistication. Information on membrane dynamics, such as conformational fluctuations, conformational changes and dynamical interactions between membrane constituents are essential for a full understanding of membrane action. Here, we review a recently developed approach aimed at obtaining such dynamical information. The approach is based on surface-specific femtosecond laser vibrational spectroscopy, and is illustrated for simple membrane model systems.     

药物小分子穿越磷脂双层膜输运过程中的时滞效应

本文基于扩散动力学,建立了一种新的药物小分子穿越磷脂双层膜输运的理论模型,研究药物小分子穿越磷脂双层膜输运的动态过程,考察药物小分子跨膜输运过程中的时间延迟(时滞)效应。研究发现,药物小分子在数分钟内穿越磷脂双层膜各区域进入细胞,由于时滞效应,穿膜过程呈现了周期性演化特性。当药物小分子数量增加到一定程度,磷脂分子层会出现微小孔,让积累的药物小分子快速通过。通过分析模型中各参数的敏感性,我们还发现,药物小分子在磷脂双层膜内不同区域的扩散特性,以及输运过程的时滞性,都会对药物小分子穿越磷脂双层膜的动力学有较大程度的影响。理论结果符合模拟、实验观测,进一步深刻揭示了药物小分子穿越磷脂双层膜的穿膜特性,可为设计确切的疗法药物提供必要的参考和新方案。     

Molecular mechanism of Peptide-induced pores in membranes

We suggest a physical mechanism by which antimicrobial peptides spontaneously induce stable pores in membranes. Peptide binding to a lipid bilayer causes an internal stress, or internal membrane tension, that can be sufficiently strong to create pores. Like detergents, peptides have a high affinity for the rim of the pore. Binding to the rims reduces the line tension and decreases the number of peptides causing the internal membrane tension. Consequently, the pore radius is stable. The pore formation resembles a phase transition.     

Neutrons for fuel cell membranes: Structure, sorption and transport properties

A molecular level understanding of structure and transport properties in fuel cell ionomer membranes is essential for designing new electrolytes with improved performance. Scattering techniques are suited tools for this purpose. In particular, neutron scattering, which has been extensively used in hydrogen-containing systems, is well adapted to investigate water-dependent complex polymeric morphologies. We report Small-Angle Neutron Scattering (SANS) studies on different types of fuel cell polymers: perfluorinated, radiation-grafted and sulfonated polyphosphazene membranes. We show that contrast variation methods can be efficiently employed to provide new insights on membrane microstructure and reveal ionic condensation effects. Neutrons have been used also as non-intrusive diagnosis tool to probe water properties and distribution inside membranes. Recently, in-situ neutronography and SANS experiments on operating fuel cells have been reported. In-plane cartography of water distribution at the surface of bipolar plates and water profiles across membrane thickness have been obtained and studied as a function of operating conditions. The last section of the article is devoted to the use of Quasi-Elastic Neutron Scattering to study water dynamics at molecular scale. We show that analysis with an appropriate sophisticated diffusion model allows to extract diffusion coefficients, characteristic times and length-scales of molecular motions. This quantitative information is fruitfully integrated in multi-scale modelling and usefully compared with numerical simulations. QENS also permits to compare alternative polymers and relate dynamical properties to chemical composition and membrane nanostructure.     

Structure of phase-inversion membranes from small-angle neutron scattering data

The structure of gradient-porous (asymmetric) membranes based on polyamide imide at different conditions of their formation has been investigated using small-angle neutron scattering. It has been shown that the membranes consist of rigid porous networks with well-defined interfaces between the polymer and the pores. It has been found that there are differences in the packings of structural elements of porous membranes-spherical pores with radii from 4 to 100 nm—depending on the membrane preformation time, drying regime, and the presence of fullerene C₆₀ for modifying the mechanical and selective properties of membranes. The membranes also contain larger pores of micrometer sizes. Differences in the rates of saturation of membranes with water and their limiting swelling ratios are found, which can be explained by the structure of the dense layers of membranes (skin layer) and their different hydrophilities (depending on the fullerene content).     

Configurations of fluid membranes and vesicles

Vesicles consisting of a bilayer membrane of amphiphilic lipid molecules are remarkably flexible surfaces that show an amazing variety of shapes of different symmetry and topology. Owing to the fluidity of the membrane, shape transitions such as budding can be induced by temperature changes or the action of optical tweezers. Thermally excited shape fluctuations are both strong and slow enough to be visible by video microscopy. Depending on the physical conditions, vesicles adhere to and unbind from each other or a substrate.

This article describes the systematic physical theory developed to understand the static and dynamic aspects of membrane and vesicle configurations. The preferred shapes arise from a competition between curvature energy, which derives from the bending elasticity of the membrane, geometrical constraints such as fixed surface area and fixed enclosed volume, and a signature of the bilayer aspect. These shapes of lowest energy are arranged into phase diagrams, which separate regions of different symmetry by continuous or discontinuous transitions. The geometrical constraints affect the fluctuations around these shapes by creating an effective tension.

For vesicles of non-spherical topology, the conformal invariance of the curvature energy leads to conformal diffusion, which signifies a one-fold degeneracy of the ground state. Unbinding and adhesion transitions arise from the balance between attractive interactions and entropic repulsion or a cost in bending energy, respectively. Both the dynamics of equilibrium fluctuations and the dynamics of shape transformations are governed not only by viscous damping in the surrounding liquid but also by internal friction if the two monolayers slip over each other. More complex membranes such as that of the red blood cell exhibit a variety of new phenomena because of coupling between internal degrees of freedom and external geometry.     

Cell deformation and increase of cytotoxicity of anticancer drugsdue to low-intensity transient electromagnetic pulses

In this paper, cell deformation induced by low-intensity electromagnetic pulses (EMPs) is presented. A broad-band transverse electromagnetic wave cell (BTEM cell) was used in the experimental system to simulate the free space transmission condition. The biological samples were exposed to the EMP field in the BTEM cell. After the chick's erythrocytes were exposed to EMP field, pores on their membranes were observed by a scanning electron microscope. Cell fusion was also found between the chick's erythrocytes as well as between the rabbit's. In other experiments, it is found that the EMP field can increase the cytotoxicity of some anticancer drugs. The results suggest that the membrane deformation is a secondary effect of electromagnetic fields     

Biomaterials and Biotechnologies Based on Nanotube Membranes

In this review, we consider materials and systems based on nanotubes formed within the pores of synthetic nanoporous membranes. The topics considered are of potential interest in the fields of biomaterials or biotechnology. There are three general membrane-based strategies that have been used to prepare materials: In the first strategy, template synthesis, nanometer scale pores are used to synthesize and modify materials. In the second strategy, we describe steps toward the design of nanotube-based membrane sensors. In the third approach, nanometer scale pores are used to separate species that translocate the membrane. In this review we consider the materials and techniques used to create, manipulate, and interrogate these bio-oriented nanotube membrane systems.     

Multiscale molecular dynamics simulations of membrane remodeling by Bin/Amphiphysin/Rvs family proteins

Membrane curvature is no longer thought of as a passive property of the membrane; rather, it is considered as an active, regulated state that serves various purposes in the cell such as between cells and organelle definition. While transport is usually mediated by tiny membrane bubbles known as vesicles or membrane tubules, such communication requires complex interplay between the lipid bilayers and cytosolic proteins such as members of the Bin/Amphiphysin/Rvs(BAR) superfamily of proteins. With rapid developments in novel experimental techniques, membrane remodeling has become a rapidly emerging new field in recent years. Molecular dynamics(MD) simulations are important tools for obtaining atomistic information regarding the structural and dynamic aspects of biological systems and for understanding the physics-related aspects. The availability of more sophisticated experimental data poses challenges to the theoretical community for developing novel theoretical and computational techniques that can be used to better interpret the experimental results to obtain further functional insights. In this review, we summarize the general mechanisms underlying membrane remodeling controlled or mediated by proteins. While studies combining experiments and molecular dynamics simulations recall existing mechanistic models, concurrently, they extend the role of different BAR domain proteins during membrane remodeling processes. We review these recent findings, focusing on how multiscale molecular dynamics simulations aid in understanding the physical basis of BAR domain proteins, as a representative of membrane-remodeling proteins.