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The phospholipase A2 (PLA2) superfamily consists of lipolytic enzymes that hydrolyze specific cell membrane phospholipids and have long been considered a central hub of biosynthetic pathways, where their lipid metabolites exert a variety of physiological roles. A misregulated PLA2 activity is associated with mainly inflammatory-derived pathologies and thus has shown relevant therapeutic potential. Many natural and synthetic anti-inflammatory drugs (AIDs) have been proposed as direct modulators of PLA2 activity. However, despite the specific chemical properties that these drugs share in common, little is known about the indirect modulation able to finely tune membrane structural changes at the precise lipid-binding site. Here, we use a novel experimental strategy based on differential scanning calorimetry to systematically study the structural properties of lipid membrane systems during PLA2 cleavage and under the influence of several AIDs. For a better understanding of the AIDs-membrane interaction, we present a comprehensive and comparative set of molecular dynamics (MD) simulations. Our thermodynamic results clearly demonstrate that PLA2 cleavage is hindered by those AIDs that significantly reduce the lipid membrane cooperativity, while the rest of the AIDs oppositely tend to catalyze PLA2 activity to different extents. On the other hand, our MD simulations support experimental results by providing atomistic details on the binding, insertion, and dynamics of each AID on a pure lipid system; the drug efficacy to impact membrane cooperativity is related to the lipid order perturbation. This work suggests a membrane-based mechanism of action for diverse AIDs against PLA2 activity and provides relevant clues that must be considered in its modulation.

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BACKGROUND: Nanomedicine and the pharmaceutical industry demand the investigation of new biomaterials to improve drug therapies. Combinations of lipids, proteins, and polymers represent innovative platforms for drug delivery. However, little is known about the interactions between such compounds and this knowledge is key to prepare successful drug delivery systems. METHODS: Biophysical properties of biohybrid vesicles (BhVs) composed of phospholipids, proteins, and amphiphilic block copolymers, assembled without using organic solvents, were investigated by differential scanning calorimetry and dynamic light scattering. We studied four biohybrid systems; two of them included the effect of incorporating tetracaine. Thermal changes of phospholipids and proteins when interacting with the amphiphilic block copolymers and tetracaine were analyzed. RESULTS: Lysozyme and the copolymers adsorb onto the lipid bilayer modifying the phase transition temperature, enthalpy change, and cooperativity. Dynamic light scattering investigations revealed relevant changes in the size and zeta potential of the BhVs. Interestingly, tetracaine, a membrane-active drug, can fluidize or rigidize BhVs. CONCLUSIONS: We conclude that positively charged regions of lysozyme are necessary to incorporate the block copolymer chains into the lipid membrane, turning the bilayer into a more rigid system. Electrostatic properties and the hydrophilic-lipophilic balance are determinant for the stability of biohybrid membranes. GENERAL SIGNIFICANCE: This investigation provides fundamental information associated with the performance of biohybrid drug delivery systems and can be of practical significance for designing more efficient drug nanocarriers.

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We demonstrate, experimentally and by molecular dynamics simulations, that krypton and xenon form nanostructured water-gas domains. High pressure was applied to force the inert gases to dissolve in water following Henry's law, then the liquid was depressurized, centrifuged, and inspected by dynamic light scattering. The observed objects have similar sizes and electrical properties to nanobubbles, but we found that they have fairly neutral buoyancy even at high gravitational fields. We posit that the formed nano objects are not bubbles but blobs, unique structures conceived as clathrate-hydrate precursors, thus resolving the so-called Laplace pressure bubble catastrophe.

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Phase transitions of liposomes are normally studied by differential scanning calorimetry. A suspension of liposomes is subjected to an increase (decrease) of temperature and when heat is absorbed (released), the liposomes transit from a gel (liquid) to a liquid (gel) phase. This endothermic (exothermic) process takes place at a temperature called the melting temperatureTm, which is distinctive of the type of lipids forming the vesicles. The vesicles, though, also modify their size in the transition. Indeed, the thickness of the membranes decreases (increases) because carbon tails misalign (align). Concomitant with the modifications in the membrane thickness, the diameter (D) of the liposomes changes too. Therefore, when they are inspected by light, the scattered signal carries information from such dilatation (contraction) process. We performed careful experiments using dynamic light scattering as a function of temperature to detect the size changes of different liposomes. Gaussian fits of the derivatives of theDvsTcurves coincide within 1% with thermograms, which hints to the possibility of performing thermodynamic studies of lipid systems employing light.

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After exciting scientific debates about its nature, the development of the exclusion zone, a region near hydrophilic surfaces from which charged colloidal particles are strongly expelled, has been finally traced back to the diffusiophoresis produced by unbalanced ion gradients. This was done by numerically solving the coupled Poisson equation for electrostatics, the two stationary Stokes equations for low Reynolds numbers in incompressible fluids, and the Nernst-Planck equation for mass transport. Recently, it has also been claimed that the leading mechanism behind the diffusiophoretic phenomenon is electrophoresis [Esplandiu et al., Soft Matter 16, 3717 (2020)]. In this paper, we analyze the evolution of the exclusion zone based on a one-component interaction model at the Langevin equation level, which leads to simple analytical expressions instead of the complex numerical scheme of previous works, yet being consistent with it. We manage to reproduce the evolution of the exclusion zone width and the mean-square displacements of colloidal particles we measure near Nafion, a perfluorinated polymer membrane material, along with all characteristic time regimes, in a unified way. Our findings are also strongly supported by complementary experiments using two parallel planar conductors kept at a fixed voltage, mimicking the hydrophilic surfaces, and some computer simulations.

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Vitrification in a dilute colloidal system needs an asymmetric particle composition (a mixture of nano and micro colloids) to materialize. The volume fraction of the large particles increases (up to ≈0.58) driven by depletion forces produced by the smaller colloids. Such entropic forces are short-ranged and attractive. We found a different type of dynamical arrest in an extremely dilute asymmetric mixture of nanovesicles and polystyrene microparticles, where energy, instead of entropy, is the main protagonist to drive the arrest. Furthermore, when the vesicles go through the gel-fluid phase transition, the mean square displacements of the microparticles suffer a sudden splitting indicating a viscous jump. If the vesicles are doped with negatively charged lipids, particles and vesicles repel each other and the rheology of the mixture becomes athermal and Newtonian. Our findings are important to understand caging phenomena in biological systems, where diverse electrostatic distributions are present.

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Combined coarse-grained (CG) and atomistic molecular dynamics (MD) simulations were performed to study the interactions of xenon with model lipid rafts consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) and cholesterol (Chol). At a concentration of 2 Xe/lipid we observed an unexpected result: spontaneous nucleation of Xe nano bubbles which rapidly plunged into the bilayer. In this process Chol, essential for raft stabilization, was pulled out from the raft into the hydrophobic zone. When concentration was further increased (3 Xe/lipid), the bubbles increase in size and disrupted both the membrane and raft. We computed the radial distribution functions, pair-wise potentials, second virial coefficients and Schlitter entropy to scrutinize the nature of the interactions. Our findings, concurring with a recent report on the origin of general anaesthesia (M. A. Pavel, E. N. Petersen, H. Wang, R. A. Lerner and S. B. Hansen, Proc. Natl. Acad. Sci. U. S. A., 2020, 117(24), 13757-13766), suggest that the well-known anaesthetic effect of Xe could be mediated by sequestration of Chol, which, in turn, compromises the stability of rafts where specialized proteins needed to produce the nervous signal are anchored.

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n-Aliphatic alcohols act as anesthetics only up to a certain chain length, beyond which its biological activity disappears. This is known as the 'cut-off' phenomenon. Although the most accepted explanation is based on action sites in membrane proteins, it is not well understood why alcohols alter their functions. The structural dependence of these protein receptors to lipid domains known as 'lipid rafts', suggests a new approach to tackle the puzzling phenomenon. In this work, by performing molecular dynamic simulations (MDS) to explore the lipid role, we provide relevant molecular details about the membrane-alcohol interaction at the cut-off point regime. Since the high variability of the cut-off points found on protein receptors in neurons may be a consequence of differences in the lipid composition surrounding such proteins, our results could have a clear-cut importance.

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Despite decades of intense research to understand the phenomenon of anesthesia and its membrane-related changes in neural transmission, where lipids and proteins have been proposed as primary targets of anesthetics, the involved action mechanisms remain unclear. Based on the overall agreement that anesthetics and neurotransmitters induce particular modifications in the plasma membrane of neurons, triggering specific responses and changes in their energetic states, we present here a thermal study to investigate membrane effects in a lipid-protein model made of 1,2-dimyristoyl-sn-glycero-3-phosphocholine and albumin from chicken egg white under the influence of neurotransmitters and anesthetics. First, we observe how ovalbumin, ovotransferrin, and lysozyme (main albumin constituents from chicken egg white) interact with the lipid membrane enhancing their lipophilic character while exposing their hydrophobic domains. This produces a lipid separation and a more ordered hybrid lipid-protein assembly. Second, we measured the thermotropic changes of this assembly induced by acetylcholine, γ-aminobutiric acid, tetracaine, and pentobarbital. Although the protein in our study is not a receptor, our results are striking, for they give evidence of the great importance of non-specific interactions in the anesthesia mechanism.

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Photo-modulation with visible light has been used to induce gains in the motility of the sperms of rabbits, boars, buffalo, bulls, fish, and humans. Although different hypotheses have been proposed to explain such an effect, the origin and mechanisms by which visible light affects sperm motility are still far from being completely understood. Several groups have observed changes in the intracellular Ca2+ concentration and significant differences in the production of ROS, which are attributed to specific photosensitizers. Also, it has been reported that blue light induces nitric oxide production in sperm cells, which plays a vital role in acrosome reaction and capacitation leading to an augmentation in the fertilisation probability. In the present work, we study the effects of green light (490-540 nm) on the sperm motility of mice. Firstly, we carried out experiments at 37 °C to confirm what previous researchers have observed before using red and blue light: that the overall sperm motility increases. Secondly, we studied the effects of green light at 10 °C and found that the motility drastically diminishes. In order to understand this opposing outcome, we carried out fluorescence measurements to evaluate reactive oxygen species production induced by green light at both temperatures. Our results suggest that the balance between the use and generation of ROS at 37 °C is favorable to the cells, while at 10 °C it is harmful.

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Local anaesthetics are among the most used drugs in clinical practice, but once they are released to the environment, the effects on the aquatic fauna remain uncertain. This study evaluates, for the first time, the impact of tetracaine, lidocaine and bupivacaine on the survival rate and physiological effects of cladocera Daphnia magna. Video-tracking and image processing allowed us to obtain changes in behaviour parameters like swimming average velocity and mean square displacement. We found that tetracaine shows the most severe effect. A high-speed microscopy system was also used to determine the response of D. magna heart to these drugs. Our results show that tetracaine presents dose-dependent area reduction during all cardiac cycle, while bupivacaine and lidocaine did not present significative effects on heart size. The tested drugs, at environmental high concentrations, altered behaviour, heart function and survival of D. magna.

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We study how cell motility affects the stains left by the evaporation of droplets of a biofluid suspension containing mouse spermatozoa. The suspension, which contains also a high concentration of salts usually needed by motile cells, forms, upon drying, a crystallized pattern. We examine the structural characteristics of such patterns by optical microscopy. The analysis reveals that cell motility affects the formation of elongated crystals with lateral tips, as well as the creation of interlocked aggregates. We prove that a lacunarity algorithm based on polar symmetry, distinguishes among deposits generated by motile and non-motile cells with an accuracy greater than 95%.

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Brownian or self-propelled particles in aqueous suspensions can be trapped by acoustic fields generated by piezoelectric transducers usually at frequencies in the megahertz. The obtained confinement allows the study of rich collective behaviours like clustering or spreading dynamics in microgravity-like conditions. The acoustic field induces the levitation of self-propelled particles and provides secondary lateral forces to capture them at nodal planes. Here, we give a step forward in the field of confined active matter, reporting levitation experiments of bacterial suspensions of Escherichia coli. Clustering of living bacteria is monitored as a function of time, where different behaviours are clearly distinguished. Upon the removal of the acoustic signal, bacteria rapidly spread, impelled by their own swimming. Nevertheless, long periods of confinement result in irreversible bacteria entanglements that could act as seeds for levitating bacterial aggregates.

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We sought to understand why saline drops produce intriguing patterns when drying in the presence of zwitterionic liposomes. Specifically, we would like to comprehend why the nature of such patterns is hierarchically driven by the Hofmeister series. The liposome suspension is made of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) with alkali metal chlorides. A complexity analysis of the patterns gives a fractal dimension around 1.71, which means that the drying process resembles a DLA mechanism. A physicochemical study, including the determination of zeta potential, molecular dynamics simulations, microrheology, and calorimetry, supports the fact that electrostatic interactions among head groups of phospholipids with alkali cations are the driven forces behind the assembling of the observed structures. Moreover, we found that the morphology of the dried droplets is sensitive to the substrate. Our findings could be used in a biological context, for example, to characterize cells in ionic media.

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The propagation of sound waves on lipid monolayers supported on water has been previously studied during the melting transition. Since changes in volume, area, and compressibility in lipid membranes have biological relevance, the observed sound propagation is of paramount importance. However, it is unknown what would occur on a lipid bilayer, which is a more approximate model of a cell membrane. With the aim to answer this relevant question, we built an experimental setup to assemble long artificial lipid membranes. We found that if these membranes are heated in order to force local melting, a thermo-mechanical perturbation propagates a long distance. Our findings may support the existence of solitary waves, postulated to explain the propagation of isentropic signals together with the action potential in neurons.

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Chromatography is, at present, the most used technique to determine the purity of alcoholic drinks. This involves a careful separation of the components of the liquid elements. However, since this technique requires sophisticated instrumentation, there are alternative techniques such as conductivity measurements and UV-Vis and infrared spectrometries. We report here a method based on salt-induced crystallization patterns formed during the evaporation of alcoholic drops. We found that droplets of different samples form different structures upon drying, which we characterize by their radial density profiles. We prove that using the dried deposit of a spirit as a control sample, our method allows us to differentiate between pure and adulterated drinks. As a proof of concept, we study tequila.

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Few years ago an article addressing the physics behind aaabstract paintings was published by Herczynski et al. (Phys. Today 64, 31 (2011) issue No. 6). The authors aimed to understand how artists like Jackson Pollock manipulated paints to create pieces of art where the theory of fluid dynamics had a clear and perceivable role. Scaling laws were found to explain the plasticity observed in the artists's traces that we admire in worldwide museums. Because sand drawings are not only wonderful artistic expressions but also intangible cultural heritages of humanity, we wonder if they could be analyzed in a similar fashion. Our goal is to explore the physics behind the formation of such drawings. In order to do so, we carry out experimental studies on the formation of sand cavities, furrows and piles, which individually or interconnected, give rise to artistic patterns. Moreover, in order to manipulate such three observables, some control parameters are needed. Altogether, they conform into simple exponential and power laws that collapse when a scaling is performed.

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The evaporation of liquid droplets deposited on a substrate is a very complex phenomenon. Driven by capillary and Marangoni flows, particle-particle and particle-substrate interactions, the deposits they leave are vestiges of such complexity. We study the formation of patterns during the evaporation of liposome suspension droplets deposited on a hydrophobic substrate at different temperatures. We observed that as we change the temperature of the substrate, a morphological phase transition occurs at a given temperature Tm. This temperature corresponds to the gel-fluid lipid melting transition of the liposome suspension. Optical microscopy and atomic force microscopy are used to study the morphology of the patterns. Based on the radial density profiles we found that all structures can be classified into two groups: patterns composed by nearly uniform deposition (below Tm) and prominent structures containing randomly distributed voids (above Tm).

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Recent studies have shown that anesthetic agents alter the physical properties of lipid rafts on model membranes. However, if this destabilization occurs in brain membranes, altering the lipid raft-protein interaction, remains unknown. We analyzed the effects produced by pentobarbital (PB) on brain plasma membranes and lipid rafts in vivo. We characterized for the first time the thermotropic behavior of plasma membranes, synaptosomes, and lipid rafts from rat brain. We found that the transition temperature from the ordered gel to disordered liquid phase of lipids is close to physiological temperature. We then studied the effect of PB on protein composition of lipid rafts. Our results show a reduction of the total protein associated to rafts, with a higher reduction of the NMDAR compared to the GABAA receptor. Both receptors are considered the main targets of PB. In general, our results suggest that lipid rafts could be plausible mediators in anesthetic action.

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We study how a magnetic bead bounces onto a horizontal diamagnetic conducting plane. The bead, falling down by gravity from a certain height, produces an Eddy current that creates a repelling force. For low velocities the bead is trapped by the surface, for intermediate ones it escapes. In such a case the induced current changes its sign, and so does the force. The balance between diamagnetic and viscoelastic interactions determines the bouncing dynamics. We find experimentally the restitution coefficient as a function of the impact speed of the bead and develop, taking into account simple energetic considerations, a model able to reproduce our findings.

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