VV-hemorphin-5 association to lipid bilayers and alterations of membrane bending rigidity

The morphinomimetic properties of hemorphins are intensively studied with regard to new peptide drug developments. In this respect, the investigation of mechanical properties and stability of lipid membranes provides a useful background for advancement in pharmacological applications of liposomes. Here we probed the effect of the endogenous heptapeptide VV-hemorphin-5 (valorphin) on the bending elasticity of biomimetic lipid membranes of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) by analysis of thermal shape fluctuations of nearly spherical giant unilamellar vesicles. In a wide concentration range covering valorphin concentrations applied in nociceptive screening in vivo, we report alterations of the bilayer bending rigidity in a concentration-dependent non-monotonic manner. We performed quantitative characterization of VV-hemorphin-5 association to POPC membranes by isothermal titration calorimetry in order to shed light on the partitioning of the amphiphilic hemorphin between the aqueous solution and membranes. The calorimetric results correlate with flicker spectroscopy findings and support the hypothesis about the strength of valorphin-membrane interaction related to the peptide bulk concentration. A higher strength of valorphin interaction with the bilayer corresponds to a more pronounced effect of the peptide on the membrane's mechanical properties. The presented study features the comprehensive analysis of membrane bending elasticity as a biomarker for physicochemical effects of peptides on lipid bilayers. The reported data on thermodynamic parameters of valorphin interactions with phosphatidylcholine bilayers and alterations of their mechanical properties is expected to be useful for applications of lipid membrane systems in pharmacology and biomedicine

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Surface Properties of Synaptosomes in the Presence of L-Glutamic and Kainic Acids: In Vitro Alteration of the ATPase and Acetylcholinesterase Activities

Morphologically and functionally identical to brain synapses, the nerve ending particles synaptosomes are biochemically derived membrane structures responsible for the transmission of neural information. Their surface and mechanical properties, measured in vitro, provide useful information about the functional activity of synapses in the brain in vivo. Glutamate and kainic acid are of particular interest because of their role in brain pathology (including causing seizure, migraine, ischemic stroke, aneurysmal subarachnoid hemorrhage, intracerebral hematoma, traumatic brain injury and stroke). The effects of the excitatory neurotransmitter L-glutamic acid and its agonist kainic acid are tested on Na+, K+-ATPase and Mg2+-ATPase activities in synaptic membranes prepared from the cerebral cortex of rat brain tissue. The surface parameters of synaptosome preparations from the cerebral cortex in the presence of L-glutamic and kainic acids are studied by microelectrophoresis for the first time. The studied neurotransmitters promote a significant increase in the electrophoretic mobility and surface electrical charge of synaptosomes at 1–4 h after isolation. The measured decrease in the bending modulus of model bimolecular membranes composed of monounsaturated lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine provides evidence for softer membranes in the presence of L-glutamate. Kainic acid does not affect membrane mechanical stability even at ten-fold higher concentrations. Both the L-glutamic and kainic acids reduce acetylcholinesterase activity and deviation from the normal functions of neurotransmission in synapses is presumed. The presented results regarding the modulation of the enzyme activity of synaptic membranes and surface properties of synaptosomes are expected by biochemical and biophysical studies to contribute to the elucidation of the molecular mechanisms of neurotransmitters/agonists’ action on membranes

Elasticité, perméabilité et morphologie des bicouches lipidiques en présence d'additifs hydrophiles et amphiphiles

On étudie les propriétés physico-chimiques des modèles lipidiques de membranes, en présence de différents additifs hydrophiles et amphiphiles. L'élasticité de courbure de vésicules géantes a été mesurée par micromanipulation et analyse des fluctuations thermiques. Les conditions expérimentales permettant la mesure des élasticités de courbure et d'expansion par micromanipulation ont été déterminées, conduisant une nouvelle méthode de mesure de la perméabilité membranaire et de la surface masquée. En particulier, l'influence de la présence de sucre en solution a été mise en évidence en étudiant l'élasticité des monocouches et des bicouches. En présence d'alaméthicine, on remarque une évolution considérable de l'élasticité de courbure et de la perméabilité de la membrane l'équilibre, ainsi que d'importants changements morphologiques lors de son adsorption asymétrique. Finalement, l'élasticité de courbure de bicouches chargées ou contenant des PEG-lipides a ét éétudiée.RENNES1-BU Sciences Philo (352382102) / SudocSudocFranceF

Micro-écoulements de vésicules : déformation et mobilité

Nous étudions expérimentalement l’écoulement de vésicules géantes dans des capillaires cylindriques. Les vésicules sont légèrement dégonflées et déformables, et les fluides interne et externe ont des viscosités voisines de celle de l’eau. Elles sont aspirées dans des capillaires en verre de diamètre voisin de la taille des vésicules et un débit constant est imposé. Des déformations significatives de la membrane se produisent, donnant aux vésicules un aspect qualitativement semblable aux formes observées pour les globules rouges dans la microcirculation ou dans les expériences d’écoulement de capsules ou les études numériques similaires (forme de balle ou de parachute). Nous présentons des mesures quantitatives de ces déformations, qui dépendent fortement du volume réduit, de la vitesse et du taux de confinement. La mobilité des vésicules (vitesse relative par rapport au fluide) est également mesurée et discutée

Bending rigidity of lipid bilayers in electrolyte solutions of sucrose

The morphology and dynamics of lipid bilayers are related to their mechanical parameters such as the bending elasticity and the intermonolayer friction. The thermal shape fluctuation analysis of nearly spherical giant lipid vesicles has been established as a versatile tool for the non-invasive measurement of the membrane bending modulus. We applied this method for probing the membrane mechanics in electrolyte solutions of sucrose. The bending rigidity of lipid membranes in aqueous solutions of mono-, di- and polysaccharides was quantified by means of a holographic tool that allows performing quantitative phase measurements for reconstituting the vesicle shape. The analysis of the time autocorrelations of vesicles’ diameters along the optical axis yields the membrane tension and bending modulus. The obtained results indicate that the presence of sodium chloride modifies the effect of sucrose on the bending rigidity of lipid bilayers. Our finding is discussed in the light of the calorimetric and molecular dynamics data in the literature about the ion-induced modification of the membrane interactions with this disaccharide. We present further evidences about the softening of lipid bilayers in sucrose-containing aqueous environment.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Digital holographic microscopy as a tool to study the thermal shape fluctuations of lipid vesicles

The bending elasticity modulus of lipid membranes is obtained by applying for the first time, to the best of our knowledge, a novel experimental technique based on digital holographic microscopy. The fluctuations of the radius with time were extracted by tracking and measuring the optical thickness at the vesicle poles. The temporal autocorrelation function of the vesicle diameter computed for each of the studied vesicles was then fitted with the theoretical expression to deduce the membrane's tension and bending constant. For the bending elasticity modulus of SOPC bilayers, the value of (0.93 ± 0.03) × 10-12 erg was obtained. This result is in accordance with values previously obtained by means of other conventional methods for the same type of lipid membrane in the presence of sugar molecules in aqueous medium. The obtained results encourage the future development of the digital holographic microscopy as a technique suitable for the measurement of the bending elasticity of lipid membranes.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Digital holographic miscroscopy as a tool to study the thermal shape fluctuations of lipid vesicles

info:eu-repo/semantics/publishe

New optical method for measuring the bending elasticity of lipid bilayers

The knowledge of the elasticity of lipid bilayer structures is fundamental for new developments in biophysics, pharmacology and biomedical research. Lipid vesicles are readily prepared in laboratory conditions and employed for studying the physical properties of lipid membranes. The thermal fluctuation analysis of the shape of lipid vesicles (or flicker spectroscopy) is one of the experimental methods widely used for the measurement of the bending modulus of lipid bilayers. We present direct phase measurements performed on dilute vesicular suspensions by means of a new optical method exploiting holographic microscopy. For the bending constant of phosphatidylcholine bilayers we report the value of 23kBT in agreement with values previously measured by micropipette aspiration, electrodeformation and flicker spectroscopy of giant lipid vesicles. The application of this novel approach for the evaluation of the bending elasticity of lipid membranes opens the way to future developments in the phase measurements on lipid vesicles for the evaluation of their mechanical constants.SCOPUS: cp.jinfo:eu-repo/semantics/publishe