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Hypothesis: Surface nanodroplets have important technological applications. Previous experiments and simulations have shown that their contact angle deviates from Young's equation. A modified version of Young's equation considering the three-phase line tension (τ) has been widely used in literature, and a wide range of values for τ are reported. We have recently shown that molecular branching affects the liquid-vapour surface tension γ lv of liquid alkanes. Therefore, the wetting behaviour of surface nanodroplets should be affected by molecular branching. This study conducted molecular dynamics (MD) simulations to gain insight into the wetting behaviour of linear and branched alkane nanodroplets on oleophilic and oleophobic surfaces. We aim to examine the Young equation's validity and branching's effect on fundamental properties, including solid-liquid surface tension γ sl and line tension τ., Simulations: The simulations were performed on a linear alkane, triacontane (C 30 H 62 ), as well as four of its branched isomers: 2,6,13,17-tetrapropyloctadecane,2,6,9,10,13,17-hexaethyloctadecane, 2,5,7,8,11,12,15-heptaethylhexadecane and 2,3,6,7,10,11-hexapropyldodecane. Nanodroplets with a diameter of approximately 15 nm were released onto the surfaces, and their contact angles were measured. Additionally, using a novel approach, the solid-liquid surface tension (γ sl ), the validity of Young's equation and line tension for all alkane and surface combinations are determined., Findings: It was discovered that the calculated γ sl , deviated from the theoretical γ sl , Young predicted from Young's equation for all alkanes on oleophilic surfaces. However, this deviation was minimal for branched alkanes on the oleophobic surfaces but more significant for the linear alkane. The findings indicated that γ sl | was lower for branched molecules and decreased as branching increased. Line tension values were then determined through a novel method, showing τ was positive for oleophilic surfaces ranging from 1.30 × 10 sl  > 0 for oleophobic surfaces. Moreover, it was observed that |γ sl N. On an oleophobic surface, linear alkane shows a negative line tension of -1.15 × 10 -10 to 6.27 × 10 -11 N. On an oleophobic surface, linear alkane shows a negative line tension of -1.15 × 10 -10 N. Line tension values between -1.15 × 10 -1 2 N are calculated for various linear alkane and surface combinations. These findings show the dependence of line tension on the contact angle and branching, demonstrating that for linear alkanes, τ is significant, whereas, for branched alkanes, line tension is smaller or negligible for large contact angles.-1 1 N. Line tension values between -1.15 × 10 -10 and + 1.1 × 10 -10 N are calculated for various linear alkane and surface combinations. These findings show the dependence of line tension on the contact angle and branching, demonstrating that for linear alkanes, τ is significant, whereas, for branched alkanes, line tension is smaller or negligible for large contact angles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The aim of this study was to investigate whether it is possible to prevent oolemma lysis after Piezo-assisted intracytoplasmic sperm injection (Piezo-ICSI) caused by abnormal membrane rupture. A total of 489 mature oocytes were obtained from 85 patients who underwent Piezo-ICSI in an infertility clinic. Inseminated oocytes were classified into the following two groups: normal rupture and abnormal rupture, and a portion of abnormally ruptured oocytes was randomly exposed to 7% PVP solution. Normal fertilization rate, degeneration rate, proportion of high-quality embryos on day 3, blastocyst formation, and morphologically high-quality blastocysts were compared. Abnormal rupture was defined as cytoplasmic membrane rupture before piezo pulse driving. Among the abnormal rupture groups, the normal fertilization and degeneration rates were compared between the high-stretched (ruptured at ≥ 50% during oocyte membrane stretching) and low-stretched (< 50% position) oocytes.The degeneration rate was significantly higher in abnormally ruptured oocytes than in normally ruptures oocytes (14.3% vs 1.3%, p < 0.001), and there was no significant difference in embryonic development after fertilization. PVP treatment immediately after oolemma rupture significantly decreased the degeneration rate (6.0% vs 19.7%, p = 0.031) and increased the normal fertilization rate. Similarly, there were no significant differences in the developmental potential. Furthermore, pregnancy outcome data showed no significant differences in pregnancy and live birth rates. The degeneration rate was reduced by treating low-stretched oocytes with PVP.Exposure to polyvinylpyrrolidone (PVP) immediately after abnormal membrane rupture represents an effective strategy to prevent oocyte degeneration. This is the first study to propose a strategy for the prevention of oocyte degeneration in Piezo-ICSI. These findings are expected to reduce the oocyte degeneration rate and increase normal fertilization rate as well as assist patients who can only acquire oocytes with weak plasma membranes., (© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)

The cell membrane, also called the plasma membrane, is the membrane on the cytoplasmic surface that separates the extracellular from the intracellular. It is thin, about 10 nm thick when viewed with an electron microscope, and is composed of two monolayers of phospholipid membranes (lipid bilayers) containing many types of proteins. It is now known that this cell membrane not only separates the extracellular from the intracellular, but is also involved in sensory stimuli such as pain, itching, sedation, and excitement. Since the "Fluid mosaic model" was proposed for cell membranes, molecules have been thought to be homogeneously distributed on the membrane surface. Later, at the end of the twentieth century, the existence of "Phase-separated microdomain structures" consisting of ordered phases rich in saturated lipids and cholesterol was suggested, and these were termed "Lipid rafts." A model in which lipid rafts regulate cell signaling has been proposed and is the subject of active research.This chapter first outlines the physicochemical properties and thermodynamic models of membrane phase separation (lipid rafts), which play an important role in cell signaling. Next, how physiologically active molecules such as local anesthetics, cooling agents (menthol), and warming agents (capsaicin) interact with artificial cell membranes will be presented.It is undeniable that the plasma membrane contains many channels and receptors that are involved in the propagation of sensory stimuli. At the same time, however, it is important to understand that the membrane exerts a significant influence on the intensity and propagation of these stimuli., (© 2024. The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.)

Condensate droplets are formed in aqueous solutions of macromolecules that undergo phase separation into two liquid phases. A well-studied example are solutions of the two polymers PEG and dextran which have been used for a long time in biochemical analysis and biotechnology. More recently, phase separation has also been observed in living cells where it leads to membrane-less or droplet-like organelles. In the latter case, the condensate droplets are enriched in certain types of proteins. Generic features of condensate droplets can be studied in simple binary mixtures, using molecular dynamics simulations. In this review, I address the interactions of condensate droplets with biomimetic and biological membranes. When a condensate droplet adheres to such a membrane, the membrane forms a contact line with the droplet and acquires a very high curvature close to this line. The contact angles along the contact line can be observed via light microscopy, lead to a classification of the possible adhesion morphologies, and determine the affinity contrast between the two coexisting liquid phases and the membrane. The remodeling processes generated by condensate droplets include wetting transitions, formation of membrane nanotubes as well as complete engulfment and endocytosis of the droplets by the membranes.

Genome replication of coronaviruses takes place in specific cellular compartments, in so-called double-membrane vesicles (DMVs), formed from the endoplasmic reticulum (ER). An intensive production of DMVs is induced by non-structural viral proteins. Here, we proposed a possible mechanism of the DMV formation from ER-derived spherical vesicles where liquid-ordered and liquid-disordered lipid phases coexist. These vesicles are supposed to divide into two homogeneous liquid-ordered and liquid-disordered vesicles. The formation of two spherical vesicles constituting DMV requires a mechanical work to be performed. We considered the excess energy of the boundary between the coexisting lipid phases as the main driving force behind the division of the initial vesicle. Explicitly accounting for the energy of elastic deformations and the interphase boundary energy, we analyzed a range of physical parameters where the DMV formation is possible. We concluded that this process can principally take place in a very narrow range of system parameters. The most probable diameter of DMVs formed according to the proposed mechanism appeared to be approximately 220 nm, in an agreement with the average diameter of DMVs observed in vivo. Our consideration predicts the DMV size to be strongly limited from above. The developed analysis can be utilized for the production of DMVs in model systems.

Line tension at phase-separated lipid domain boundaries is an important factor that governs the stability of the phase separation. We studied the control of the line tension in lipid membranes composed of dioleoylphosphocholine (DOPC), dipalmitoylphosphocholine (DPPC), and cholesterol (Chol) by the addition of the following three monounsaturated fatty acids (MUFAs) with different chain lengths: palmitoleic acid (PaA), oleic acid (OA), and eicosenoic acid (EiA). In addition, we attempted to alter the line tension by applying osmotic pressure. The phase behavior of the MUFA-containing lipid membranes in the presence and absence of osmotic stress was observed by fluorescence and confocal laser scanning microscopy. The line tension was quantitatively measured from the domain boundary fluctuation by flicker spectroscopy, and the interactions between the lipids and MUFAs were examined by differential scanning calorimetry. PaA and OA, which are shorter MUFAs, decreased the line tension, whereas EiA changed the liquid domain to a solid domain. The osmotic pressure increased the line tension, even in the presence of MUFAs. It may be possible to control the line tension by combining the chemical approach of MUFA addition and the physical approach of applying osmotic pressure.

Lipids extracted from Purified Myelin Membranes (LPMM) were spread as monomolecular films at the air/aqueous interface. The films were visualized by Brewster Angle Microscopy (BAM) at different lateral pressures (π) and ionic environments. Coexistence of Liquid-Expanded (LE) and cholesterol-enriched (CE) rounded domains persisted up to π ≈ 5 mN/m but the monolayers became homogeneous at higher surface pressures. Before mixing, the domains distorted to non-rounded domains. We experimentally measured the line tension (λ) for the lipid monolayers at the domain borders by a shape relaxation technique using non-homogeneous electric fields. Regardless of the subphase conditions, the obtained line tensions are of the order of pN and tended to decrease as lateral pressure increased toward the mixing point. From the mean square displacement of nested trapped domains, we also calculated the dipole density difference between phases (μ). A non-linear drop was detected in this parameter as the mixing point is approached. Here we quantitively evaluated the π-dependance of both parameters with proper power laws in the vicinity of the critical mixing surface pressure, and the exponents showed to be consistent with a critical phenomenon in the two-dimensional Ising universality class. This idea of bidimensionality was found to be compatible only for simplified lipidic systems, while for whole myelin monolayers, that means including proteins, no critical mixing point was detected. Finally, the line tension values were related with the thickness differences between phases (Δt) near the critical point., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Despite considerable research efforts, the influence of contact line tension during wetting at the nanoscale and its experimental determination remain challenging tasks. So far, molecular dynamics simulations and atomic force microscope measurements have contributed to the understanding of these phenomena. However, a direct measurement of the size dependence of the contact angle and the magnitude of the apparent line tension has not been realized so far. Here, we show that the contact angle is indeed dependent on the drop size for small drop diameters and determine the magnitude of the apparent line tension via liquid-metal based measurements of advancing and receding contact angle inside a scanning electron microscope. For this purpose, a robotic setup inside an electron microscope chamber and oxide-free Galinstan droplets-produced via an electromigration-based and focused ion beam irradiation-assisted process-are employed. Using the first-order correction of Young's equation, we find an apparent line tension value of 4.02 × 10 -7 J/m for Galinstan© on stainless steel.

We investigated the wetting transitions of tetradecane and hexadecane droplets in dodecyltrimethylammonium bromide (C12TAB), tetradecyltrimethylammonium bromide (C14TAB), and hexadecyltrimethylammonium bromide (C16TAB) aqueous solutions. By varying the surfactant concentration, the formation of mixed monolayers of a surfactant and an alkane was observed at the air-water interface. Depending on the combination of surfactant and alkane, these wetting monolayers underwent another thermal phase transition upon cooling either to a frozen mixed monolayer (S1) or a bilayer structure composed of a solid monolayer of a pure alkane rested on a liquid-like mixed monolayer (S2). Based on the phase diagrams determined by phase modulation ellipsometry, the difference in the morphology of the nucleated S1 and S2 phase domains was also investigated using Brewster angle microscopy. Domains of the S1 phase were relatively small and highly branched, whereas those of the S2 phase were large and circular. The difference in domain morphology was explained by the competition of the domain line tension and electrostatic dipole interactions between surfactant molecules in the domains.

Purified myelin membranes (PMM) were spread as monomolecular films at the air/aqueous solution interface, and visualized by Brewster Angle Microscopy (BAM) at different lateral pressures (π) on three specific aqueous solutions: absence of salts, physiological conditions and presence of calcium. Coexistence of Liquid-Expanded (LE) and Liquid Ordered (LO) phases persisted up to collapse in the presence of salts, whereas monolayers became homogeneous at π ≥ 35-40 mN/m when salts are absent. This PMM phase-mixing behavior in monolayers is similar to the previously reported behavior of PMM multilamellar vesicles. Reflectivities (R p ) of p-polarized light from both phases were assessed throughout the whole π -range, and film thicknesses (t) were calculated from the R p values and measured film refractive indices (n). The LO phase was found to be more reflective and thicker than the LE phase at π ≤ 15 mN/m, but less reflective and thinner at higher π. We also determined the line tension (λ) of PMM monolayers at the domain boundaries from the rate of domain shape relaxation, which turned out to be of the order of picoNewtons (pN) and decreased as π increased. A correlation between λ and thickness differences (Δt) was found, suggesting that Δt is a molecular determinant for λ in PMM monolayers. Both λ and Δt were found to increase markedly when calcium was present in the subphase. This result corroborates the concept of divalent cations as a stabilizing factor for phase separation, in line with earlier studies on this mixture forming multilamellar membrane arrangements., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Four-component phase diagrams reveal that Liquid-disordered + liquid-ordered (Ld + Lo) nanodomains are exclusively found adjacent to a three-phase region, and so cannot be a one-phase microemulsion. Of importance for understanding biological membranes, a small change in lipid bilayer composition can change the size of these coexisting phase domains hundreds of fold, between tens of nanometers and microns. Nanodomain diameter, measured from small angle neutron scattering, is in the range 15-35 nm, consistent with stabilization by repulsive dipole fields. Ld/Lo line tension controls the Ld + Lo domain size transition. Other than size, chemical and physical properties of the phase domains do not seem to change during the transition. Unfavorable lipid-lipid pairwise interactions, rather than phase thickness mismatch, seem to be the main reason for Ld + Lo immiscibility. Pairwise interactions of cholesterol-phospholipid seem to be favorable, whereas pairwise interactions of high-melting phospholipid with low-melting phospholipid are unfavorable. Measured Ld/Lo line tension, like the phase separation, is created mainly by unfavorable lipid-lipid pairwise interactions. Lipid dipole-dipole repulsion opposes these unfavorable lipid-lipid pairwise interactions and thus, in a sense, is the reason that nanodomains form. Bilayer physical and chemical properties measured from macroscopic domains of coexisting Ld + Lo phases should be good approximations for the properties of coexisting nanoscopic domains., (Copyright © 2021. Published by Elsevier B.V.)

Recent experiments have shown that certain molecular agents can selectively penetrate and aggregate in bacterial lipid membranes, leading to their permeability and rupture. To help reveal and understand the underlying mechanisms, here we establish a theory to show that the deformation energy of the membrane tends to limit the growth of molecular domains on a lipid membrane, resulting in a characteristic domain size, and that the domain aggregation significantly reduces the energy barrier to pore growth. Coarse-grained molecular dynamics simulations are performed to validate such domain aggregation and associated pore formation. This study sheds light on how lipid membranes can be damaged through molecular domain aggregation and contributes to establish a theoretical foundation for the next-generation membrane-targeting nanomedicine.

Nucleation and growth is a technique widely used to prepare colloids, in which droplets are adsorbed onto substrate particles. Changing the contact angle of the substrates can greatly alter the morphology of the product particles. Here, we investigate the nucleation and growth of 3-methacryloxypropyltrimethoxysilane (MPTMS) both onto Stöber spheres and onto (cross-linked) MPTMS* spheres. The former results in 'snowman' particles with a cap-shaped MPTMS* compartment, and we show that their morphology is highly controllable via the MPTMS content in the reaction mixture. The contact angle of the MPTMS* compartment decreases with droplet diameter, suggesting that this wetting process is affected not only by surface tension but also by line tension. In contrast to Stöber spheres, MPTMS* substrate particles yield highly reproducible and tuneable 'engulfed-sphere' colloids with an internal reference axis (but a homogeneous mass distribution). These engulfed-sphere particles can be fully index-matched for confocal microscopy on account of their homogeneous refractive index. Suitable index-matching mixtures of polar and of low-polar media are presented, where cyclohexyl iodide (CHI) is introduced as a new medium for colloids of high refractive index. Finally, the index-matched engulfed-sphere colloids are self-assembled into (close-packed and long-range) plastic phases, and the particles' rotational diffusion inside the crystal phases is tracked via confocal microscopy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Inc.)

A triangular lattice model for pattern formation by core-shell particles at fluid interfaces is introduced and studied for the particle to core diameter ratio equal to 3. Repulsion for overlapping shells and attraction at larger distances due to capillary forces are assumed. Ground states and thermodynamic properties are determined analytically and by Monte Carlo simulations for soft outer- and stiffer inner shells, with different decay rates of the interparticle repulsion. We find that thermodynamic properties are qualitatively the same for slow and for fast decay of the repulsive potential, but the ordered phases are stable for temperature ranges, depending strongly on the shape of the repulsive potential. More importantly, there are two types of patterns formed for fixed chemical potential-one for a slow and another one for a fast decay of the repulsion at small distances. In the first case, two different patterns-for example clusters or stripes-occur with the same probability for some range of the chemical potential. For a fixed concentration, an interface is formed between two ordered phases with the closest concentration, and the surface tension takes the same value for all stable interfaces. In the case of degeneracy, a stable interface cannot be formed for one out of four combinations of the coexisting phases, because of a larger surface tension. Our results show that by tuning the architecture of a thick polymeric shell, many different patterns can be obtained for a sufficiently low temperature.

Unsaturated and saturated phospholipids tend to laterally segregate, especially in the presence of cholesterol. Small molecules such as neurotransmitters, toxins, drugs etc. possibly modulate this lateral segregation. The small aromatic neurotransmitter serotonin (5-HT) has been found to bind to membranes. We studied the lipid structure and packing of a ternary membrane mixture consisting of palmitoyl-oleoyl-phosphatidylcholine, palmitoyl-sphingomyelin, and cholesterol at a molar ratio of 4/4/2 in the absence and in the presence of 5-HT, using a combination of solid-state 2 H NMR, atomic force microscopy, and atomistic molecular dynamics (MD) simulations. Both NMR and MD report formation of a liquid ordered (L o ) and a liquid disordered (L d ) phase coexistence with small domains. Lipid exchange between the domains was fast such that single component 2 H NMR spectra are detected over a wide temperature range. A drastic restructuring of the domains was induced when 5-HT is added to the membranes at a 9 mol% concentration relative to the lipids. 2 H NMR spectra of all components of the mixture showed two prominent contributions indicative of molecules of the same kind residing both in the disordered and the ordered phase. Compared to the data in the absence of 5-HT, the lipid chain order in the disordered phase was further decreased in the presence of 5-HT. Likewise, addition of serotonin increased lipid chain order within the ordered phase. These characteristic lipid chain order changes were confirmed by MD simulations. The 5-HT-induced larger difference in lipid chain order results in more pronounced differences in the hydrophobic thickness of the individual membrane domains. The correspondingly enlarged hydrophobic mismatch between ordered and disordered phases is assumed to increase the line tension at the domain boundary, which drives the system into formation of larger size domains. These results not only demonstrate that small membrane binding molecules such as neurotransmitters have a profound impact on essential membrane properties. It also suggests a mechanism by which the interaction of small molecules with membranes can influence the function of membrane proteins and non-cognate receptors. Altered membrane properties may modify lateral sorting of membrane protein, membrane protein conformation, and thus influence their function as suspected for neurotransmitters, local anesthetics, and other small drug molecules., (Copyright © 2020 Engberg, Bochicchio, Brandner, Gupta, Dey, Böckmann, Maiti and Huster.)

We use phase contrast microscopy of red blood cells to observe the transition between the initial discocyte shape and a spiculated echinocyte form. During the early stages of this change, spicules can move across the surface of the cell; individual spicules can also split apart into pairs. One possible explanation of this behaviour is that the membrane forms large scale domains in association with the spicules. The spicules are formed initially at the rim of the cell and then move at speeds of up to 3 μm/min towards the centre of the disc. Spicule formation that was reversed and then allowed to proceed a second time resulted in spicules at reproducible places, a shape memory effect that implies that the cytoskeleton contributes towards stopping the spicule movement. The splitting of the spicules produces a well-defined shape change with an increase in membrane curvature associated with formation of the daughter pair of spicules; the total boundary length around the spicules also increases. Following the model in which the spicules are associated with lipid domains, these observations suggest an experimental procedure that could potentially be applied to the calculation of the line tension of lipid domains in living cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Triangular lattice models for pattern formation by hard-core soft-shell particles at interfaces are introduced and studied in order to determine the effect of the shell thickness and structure. In model I, we consider particles with hard-cores covered by shells of cross-linked polymeric chains. In model II, such inner shell is covered by a much softer outer shell. In both models, the hard cores can occupy sites of the triangular lattice, and nearest-neighbor repulsion following from overlapping shells is assumed. The capillary force is represented by the second or the fifth neighbor attraction in model I or II, respectively. Ground states with fixed chemical potential μ or with fixed fraction of occupied sites c are thoroughly studied. For T > 0, the μ ( c ) isotherms, compressibility and specific heat are calculated by Monte Carlo simulations. In model II, 6 ordered periodic patterns occur in addition to 4 phases found in model I. These additional phases, however, are stable only at the phase coexistence lines at the ( μ , T ) diagram, which otherwise looks like the diagram of model I. In the canonical ensemble, these 6 phases and interfaces between them appear in model II for large intervals of c and the number of possible patterns is much larger than in model I. We calculated line tensions for different interfaces, and found that the favorable orientation of the interface corresponds to its smoothest shape in both models., (Creative Commons Attribution license.)

The large plasticity, dynamics and adaptability of biological membranes allow different modes of intrinsic and inducible permeability. These phenomena are of physiological importance for a number of natural functions related to cell death and can also be manipulated artificially for practical purposes like gene transfer, drug delivery, prevention of infections or anticancer therapy. For these advances to develop in a controllable and specific way, we need a sufficient understanding of the membrane permeability phenomena. Since the formulation of early concepts of pore formation, there has been an enormous effort to describe membrane permeability by using theory, simulations and experiments. A major breakthrough has come recently through theoretical developments that allow building continuous trajectories of pore formation both in the absence and presence of stress conditions. The new model provides a coherent quantitative view of membrane permeabilization, useful to test the impact of known lipid properties, make predictions and postulate specific pore intermediates that can be studied by simulations. For example, this theory predicts unprecedented dependencies of the line tension on the pore radius and on applied lateral tension which explain previous puzzling results. In parallel, important concepts have also come from molecular dynamics simulations, of which the role of water for membrane permeabilization is of special interest. These advances open new challenges and perspectives for future progress in the study of membrane permeability, as experiments and simulations will need to test the theoretical predictions, while theory achieves new refinements that provide a physical ground for observations.

Chemically simplified lipid mixtures are used here as models of the cell plasma membrane exoplasmic leaflet. In such models, phase separation and morphology transitions controlled by line tension in the liquid-disordered (Ld) + liquid-ordered (Lo) coexistence regime have been described [1]. Here, we study two four-component lipid mixtures at different cholesterol fractions: brain sphingomyelin (BSM) or 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/cholesterol (Chol). On giant unilamellar vesicles (GUVs) display a nanoscopic-to-macroscopic transition of Ld + Lo phase domains as POPC is replaced by DOPC, and this transition also depends on the cholesterol fraction. Line tension decreases with increasing cholesterol mole fractions in both lipid mixtures. For the ternary BSM/DOPC/Chol mixture, the published phase diagram [19] requires a modification to show that when cholesterol mole fraction is >~0.33, coexisting phase domains become nanoscopic., (Copyright © 2018 Elsevier B.V. All rights reserved.)

AFM is now established as a powerful and direct technique for studying lipid membranes, and is highly complementary with other techniques. It is the only method for direct imaging and mechanical probing of lipid phase structure in a liquid environment down to the nanometer level. In order to understand the structure, function, and interactions of membranes at this level, we must be able to reliably and quantitatively measure the AFM images. Here we describe the methods used to process and analyze AFM images of phase-separated supported lipid bilayers . This initially takes a static approach, where we simply quantify the % of domain area, number of domains, and morphology, and quantify how many images must be taken to obtain reliable statistics. We then look at dynamics, describing the methods we use to study the nanometer scale motion of the domain perimeter as observed using Fast Scan AFM, and hence extract a quantitative line tension.

The response of biomembranes to aqueous-phase separation and to the resulting water-in-water droplets has been recently studied on the micrometer scale using optical microscopy and elasticity theory. When such a droplet adheres to the membrane, it forms a contact area that is bounded by a contact line. For a micrometer-sized droplet, the line tension associated with this contact line can usually be ignored compared with the surface tensions. However, for a small nanoscopic droplet, this line tension is expected to affect the membrane-droplet morphology. Here, we use molecular simulations to study nanodroplets at membranes and to gain insight into these line tension effects. The latter effects are shown to depend strongly on another key parameter, the mechanical tension experienced by the membrane. For a large membrane tension, a droplet adhering to the membrane is only partially engulfed by the membrane, and the membrane-droplet system exhibits an axisymmetric morphology. A reduction of the membrane tension leads to an increase in the contact area and a decrease in the interfacial area of the droplet, initially retaining its axisymmetric shape, which implies a circular contact line and a circular membrane neck. However, when the tension falls below a certain threshold value, the system undergoes a morphological transition toward a non-axisymmetric morphology with a non-circular membrane neck. This morphology persists until the nanodroplet is completely engulfed by the membrane and the membrane neck has closed into a tight-lipped shape. The latter morphology is caused by a negative line tension, which is shown to be a robust feature of membrane-droplet systems. A closed membrane neck with a tight-lipped shape suppresses both thermally activated and protein-induced scission of the neck, implying a reduction in the cellular uptake of nanodroplets by pinocytosis and fluid-phase endocytosis. Furthermore, based on our results, we can also draw important conclusions about the time-dependent processes corresponding to the surface nucleation and growth of nanodroplets at membranes.

The notion of three-phase (line) tension remains one of the most disputable notions in surface science. A very broad range of its values has been reported. Experts even do not agree on the sign of line tension. The polymer-chain-like model of three-phase (triple) line enables rough estimation of entropic input into the value of line tension, estimated as Γ e n ≅ k B T d m ≅ 10 - 11 N , where d m is the diameter of the liquid molecule. The introduction of the polymer-chain-like model of the triple line is justified by the "water string" model of the liquid state, predicting strong orientation effects for liquid molecules located near hydrophobic moieties. The estimated value of the entropic input into the line tension is close to experimental findings, reported by various groups, and seems to be relevant for the understanding of elastic properties of biological membranes.

Core-shell nanoparticles consisting of silica as core and surface-grafted poly(dimethylsiloxane) (PDMS) as shell with different diameters were prepared and used as heterogeneous nucleation agents to obtain CO 2 -blown poly(methyl methacrylate) (PMMA) nanocomposite foams. PDMS was selected as the shell material as it possesses a low surface energy and high CO 2 -philicity. The successful synthesis of core-shell nanoparticles was confirmed by Fourier transform infrared spectroscopy, thermogravimetric analysis, and transmission electron microscopy. The cell size and cell density of the PMMA micro- and nanocellular materials were determined by scanning electron microscopy. The cell nucleation efficiency using core-shell nanoparticles was significantly enhanced when compared to that of unmodified silica. The highest nucleation efficiency observed had a value of ∼0.5 for nanoparticles with a core diameter of 80 nm. The particle size dependence of cell nucleation efficiency is discussed taking into account line tension effects. Complete engulfment by the polymer matrix of particles with a core diameter below 40 nm at the cell wall interface was observed corresponding to line tension values of approximately 0.42 nN. This line tension significantly increases the energy barrier of heterogeneous nucleation and thus reduces the nucleation efficiency. The increase of the CO 2 saturation pressure to 300 bar prior to batch foaming resulted in an increased line tension length. We observed a decrease of the heterogeneous nucleation efficiency for foaming after saturation with CO 2 at 300 bar, which we attribute to homogenous nucleation becoming more favorable at the expense of heterogeneous nucleation in this case. Overall, it is shown that the contribution of line tension to the free energy barrier of heterogeneous foam cell nucleation must be considered to understand foaming of viscoelastic materials. This finding emphasizes the need for new strategies including the use of designer nucleating particles to enhance the foam cell nucleation efficiency.

The functional mechanisms of local anesthetics (LAs) have not yet been fully explained, despite their importance in modern medicine. Recently, an indirect interaction between channel proteins and LAs was proposed as follows: LAs alter the physical properties of lipid membranes, thus affecting the channel proteins. To examine this hypothesis, we investigated changes in thermal stability in lipid membranes consisting of dioleoylphosphocholine, dipalmitoylphosphocholine, and cholesterol by adding the LAs, lidocaine and tetracaine. The miscibility temperature of liquid-ordered (L o ) and liquid-disordered (L d ) phase separation was lowered, whereas that of phase separation between solid-ordered (S o ) and L d phases was unchanged by LAs. Furthermore, we measured the line tension at the L o /L d interface from domain boundary fluctuation and found that it was significantly decreased by LAs. Finally, differential scanning calorimetry (DSC) revealed a change in the lipid main transition temperature on the addition of LAs. Based on the DSC measurements, we considered that LAs are partitioned into two coexisting phases., Competing Interests: The authors declare no conflicts of interest.

A Finsler geometric surface model is studied as a coarse-grained model for membranes of three components, such as zwitterionic phospholipid (DOPC), lipid (DPPC) and an organic molecule (cholesterol). To understand the phase separation of liquid-ordered (DPPC rich) L o and liquid-disordered (DOPC rich) L d , we introduce a binary variable σ ( = ± 1 ) into the triangulated surface model. We numerically determine that two circular and stripe domains appear on the surface. The dependence of the morphological change on the area fraction of L o is consistent with existing experimental results. This provides us with a clear understanding of the origin of the line tension energy, which has been used to understand these morphological changes in three-component membranes. In addition to these two circular and stripe domains, a raft-like domain and budding domain are also observed, and the several corresponding phase diagrams are obtained.

The overall goal of this work is to study the combined effects of Mini-B, a 34 residue synthetic analog of the lung surfactant protein SP-B, and cholesterol, a neutral lipid, on a model binary lipid mixture containing dipalmitolphosphatidylcholine (DPPC) and palmitoyl-oleoyl-phosphatidylglycerol (POPG), that is often used to mimic the primary phospholipid composition of lung surfactants. Using surface pressure vs. mean molecular area isotherms, fluorescence imaging and analysis of lipid domain size distributions; we report on changes in the structure, function and stability of the model lipid-protein films in the presence and absence of varying composition of cholesterol. Our results indicate that at low cholesterol concentrations, Mini-B can prevent cholesterol's tendency to lower the line tension between lipid domain boundaries, while maintaining Mini-B's ability to cause reversible collapse resulting in the formation of surface associated reservoirs. Our results also show that lowering the line tension between domains can adversely impact monolayer folding mechanisms. We propose that small amounts of cholesterol and synthetic protein Mini-B can together achieve the seemingly opposing requirements of efficient LS: fluid enough to flow at the air-water interface, while being rigid enough to oppose irreversible collapse at ultra-low surface tensions., (Copyright © 2016 Elsevier B.V. All rights reserved)

Many water-soluble cationic porphyrins are known to be prospective chemotherapeutics and photosensitizers for cancer treatment and diagnosis. The physicochemical properties of porphyrins, in particular their interactions with membranes, are important determining factors of their biological activity. The influence of cationic meso-tetra-[4-N-(2'-hydroxyethyl) pyridyl] porphyrin (H2TOEtPyP) on the stability and conductivity of bilayer lipid membranes (BLMs) was studied. H2TOEtPyP4 porphyrin was shown to decrease the stability of BLMs made of a mixture of DOPS and DPPE (1:1) in an electric field because of a reduction of line tension of spontaneously formed pore edges in the BLM. The presence of cationic porphyrin was found to reduce BLM surface tension. This effect was enhanced with increasing porphyrin concentration. H2TOEtPyP4 increased the probability of spontaneous pore formation. Further investigating the cyclic current-voltage characteristics of BLMs allowed determining the electrical capacity and conductivity of BLMs in the presence of H2TOEtPyP4 porphyrin. It was shown that in the presence of cationic porphyrin the electrical capacity as well as conductivity of the BLM increases.

Membrane damage is a daily threat to the life of a cell, especially cells from muscles, gut, epidermis and vasculature, tissues that are particularly subjected to mechanical stress. Damages can come from different sources and give rise to different holes in terms of size and nature. For example, while some holes are simply scratches in the lipid bilayer, others are delimited by pore forming proteins. It is thus expectable that these wounds will not evolve similarly in a cellular context, and that repair mechanisms will differ to a certain extent. It would therefore be misleading to fully generalize cell membrane damage and repair, and consider it as one universal phenomenon. Indeed, damage has been observed in cells ranging from the rather small mammalian cells (∼30μm) to the very big Urchin egg (∼100μm). Moreover, the wounds observed or artificially induced in eukaryotic cells range from some nanometers to several micrometers, and can be delimited by particular molecules as mentioned before. This chapter aims at reviewing the different physico-chemical and biological parameters that can influence wound evolution in cells and to conciliate the different repair mechanisms that have been described by evaluating them in their cellular and wound type context., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Ionic liquids (ILs) are a unique family of molecular liquids ('molten salts') that consist of a combination of bulky organic cations coupled to inorganic or organic anions. The net result of steric hindrance and strong hydrogen bonding between components results in a material that is liquid at room temperature. One can alter the properties of ionic liquids through chemical modification of anion and cation, thus tailoring the IL for a given application. One such property that can be controlled or selected is the wettability of an IL on a particular solid substrate. However, the study of wetting of ionic liquids is complicated by the care required for accurate and reproducible measurement, due to both the susceptibility of the IL properties to water content, as well as to the sensitivity of wettability measurements to the state of the solid surface. This review deals with wetting studies of ILs to date, including both static and dynamic wetting, as well as issues concerning line tension and the formation of precursor and wetting films., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The observation by Atomic Force Microscopy of a range of nanophases on hydrophobic surfaces poses some challenging questions, not only related to the stability of these objects but also regarding their wetting properties. Spherical capped nanobubbles are observed to exhibit contact angles that far exceed the macroscopic contact angle measured for the same materials, whereas nanodroplets exhibit contact angles that are much the same as the macroscopic contact angle. Micropancakes are reported to consist of gas, in which case their wetting properties are mysterious. They should only be stable when the van der Waals forces act to thicken the film whereas for a gas, the van der Waals forces will always act to thin the film. Here we examine the available evidence and contribute some additional experiments in order to review our understanding of the wetting properties of these nanophases. We demonstrate that if in fact micropancakes consist of a contaminant their wetting properties can be explained, though the very high contact angles of nanobubbles remain unexplained., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Alkane droplets on aqueous solutions of surfactants exhibit a first-order wetting transition as the concentration of surfactant is increased. The low-concentration or "partial wetting" state corresponds to an oil lens in equilibrium with a two-dimensional dilute gas of oil and surfactant molecules. The high-concentration or "pseudo-partial wetting" state consists of an oil lens in equilibrium with a mixed monolayer of surfactant and oil. Depending on the combination of surfactant and oil, these mixed monolayers undergo a thermal phase transition upon cooling, either to a frozen mixed monolayer or to an unusual bilayer structure in which the upper leaflet is a solid layer of pure alkane with hexagonal packing and upright chains while the lower leaflet remains a disordered liquid-like mixed monolayer. Additionally, certain long-chain alkanes exhibit a surface freezing transition at the air-oil interface where the top monolayer of oil freezes above its melting point. In this review, we summarize our previous studies and discuss how these wetting and surface freezing transitions influence the line tension of oil lenses from both an experimental and theoretical perspective., (© 2013 Elsevier B.V. All rights reserved.)

The orientational texture of gel-phase lipid bilayers is a phenomenon that can structure membrane domains. Using two-photon polarized fluorescence microscopy and image analysis, we map the lateral variation of the lipid orientation (the texture) in single domains. With this method, we uncover a lipid-induced transition between vortex and uniform textures in binary phospholipid bilayers. By tuning the lipid composition, the hydrophobic mismatch at the domain boundary can be varied systematically as monitored by AFM. Low hydrophobic mismatch correlates with domains having uniform texture, while higher mismatch values correlate with a vortex-type texture. The defect pattern created during early growth persists in larger domains, and a minimal model incorporating the anisotropic line tension and the vortex energy can rationalize this finding. The results suggest that the lipid composition and the domain nucleation process are critical factors that determine the texture pattern of membrane domains.

Alkanes on surfactant solutions can form three distinct phases at the air-solution interface, a liquid phase (L), a solid monolayer phase (S1), and a hybrid bilayer phase (S2). Phase coexistence between any two, or all three, of these phases has been observed by Brewster angle microscopy of tetradecane, hexadecane, and their mixtures on solutions of tetradecyltrimethylammonium bromide. The morphologies of the domains depend on the competition between line tension and electrostatic interactions, which are essentially different depending on the pair of phases in contact. Domains of S1 in the L phase are long and thin; however, long, thin domains of L in an S1 phase are not stable but break up into a string of small circular domains. The bilayer S2 domains are always circular, owing to the dominance of line tension on the morphology.