Absorption of the [bmim][Cl] Ionic Liquid in DMPC Lipid Bilayers across Their Gel, Ripple, and Fluid Phases

Lipid bilayers are a key component of cell membranes and play a crucial role in life and in bio-nanotechnology. As a result, controlling their physicochemical properties holds the promise of effective therapeutic strategies. Ionic liquids (ILs)-a vast class of complex organic electrolytes-have shown a high degree of affinity with lipid bilayers and can be exploited in this context. However, the chemical physics of IL absorption and partitioning into lipid bilayers is yet to be fully understood. This work focuses on the absorption of the model IL [bmim] [Cl] into 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayers across their gel, ripple, and fluid phases. Here, by small-angle neutron scattering, we show that (i) the IL cations are absorbed in the lipid bilayer in all its thermodynamic phases and (ii) the amount of IL inserted into the lipid phase increased with increasing temperature, changing from three to four IL cations per 10 lipids with increasing temperature from 10 degrees C in the gel phase to 40 degrees C in the liquid phase, respectively. An explicative hypothesis, based on the entropy gain coming from the IL hydration water, is presented to explain the observed temperature trend. The ability to control IL absorption with temperature can be used as a handle to tune the effect of ILs on biomembranes and can be exploited in bio-nanotechnological applications

Reproductive Coercion and Relationship Abuse Among Adolescents and Young Women Seeking Care at School Health Centers.

ObjectiveTo investigate demographic differences and evaluate how reproductive coercion and relationship abuse influences young females' care-seeking and sexual health behaviors.MethodsWe conducted a secondary analysis of cross-sectional baseline survey data from sexually active female students (aged 14-19 years) who sought care from school health centers. Outcomes included recent (previous 3 months) reproductive coercion, physical or sexual adolescent relationship abuse, and nonpartner sexual violence victimization. Cluster-adjusted χ tests compared demographics and generalized linear mixed models estimated associations among reproductive coercion, adolescent relationship abuse (physical and sexual abuse in romantic relationships), and care-seeking and sexual health behaviors.ResultsOf 550 sexually active high school females, 12% reported recent reproductive coercion and 17% reported physical or sexual adolescent relationship abuse, with no significant demographic differences. Prevalence of recent nonpartner sexual violence was 17%. There were no observed significant differences in care-seeking behaviors among those with recent reproductive coercion compared with those without. Physical or sexual adolescent relationship abuse was associated with increased odds of seeking testing or treatment for sexually transmitted infections (adjusted odds ratio [aOR] 2.08, 95% CI 1.05-4.13). Females exposed to both adolescent relationship abuse and reproductive coercion had higher odds of having a partner who was 5 or more years older (aOR 4.66, 95% CI 1.51-14.4), having two or more recent sexual partners (aOR 3.86, 95% CI 1.57-9.48), and using hormonal contraception only (aOR 3.77, 95% CI 1.09-13.1 vs hormonal methods with condoms).ConclusionAlmost one in eight females experienced recent reproductive coercion. We did not observe significant demographic differences in reproductive coercion. Partner age and number of sexual partners may elevate risk for abusive relationships. Relationship abuse is prevalent among high school students seeking care, with no clear pattern for case identification. By failing to identify factors associated with harmful partner behaviors, our results support universal assessment for reproductive coercion and relationship abuse among high school-aged adolescents, involving education, resources, and harm-reduction counseling to all patients.Clinical trial registrationClinicalTrials.gov, NCT01678378

The H I mass function of group galaxies in the ALFALFA survey

We estimate the H i mass function (HIMF) of galaxies in groups based on thousands of ALFALFA (Arecibo Legacy Fast ALFA survey) H i detections within the galaxy groups of four widely used SDSS (Sloan Digital Sky Survey) group catalogues. Although differences between the catalogues mean that there is no one definitive group galaxy HIMF, in general we find that the low-mass slope is flat, in agreement with studies based on small samples of individual groups, and that the 'knee' mass is slightly higher than that of the global HIMF of the full ALFALFA sample. We find that the observed fraction of ALFALFA galaxies in groups is approximately 22 per cent. These group galaxies were removed from the full ALFALFA source catalogue to calculate the field HIMF using the remaining galaxies. Comparison between the field and group HIMFs reveals that group galaxies make only a small contribution to the global HIMF as most ALFALFA galaxies are in the field, but beyond the HIMF 'knee' group galaxies dominate. Finally, we attempt to separate the group galaxy HIMF into bins of group halo mass, but find that too few low-mass galaxies are detected in the most massive groups to tightly constrain the slope, owing to the rarity of such groups in the nearby Universe where low-mass galaxies are detectable with existing H i surveys.© 2020 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical SocietyWe acknowledge the work of the entire ALFALFA team for observing, flagging, and performing signal extraction. We thank the anonymous referee for their suggestions that helped to improve this paper. MGJ is supported by a Juan de la Cierva formacion´ fellowship (FJCI-2016-29685) from the Spanish Ministerio de Ciencia, Innovacion y Universidades (MCIU). MGJ and LVM ´ also acknowledge support from the grants AYA2015-65973-C3-1- R (MINECO/FEDER, UE) and RTI2018-096228-B-C31 (MCIU). The research of KMH is supported by the under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement nr. 291531. EAKA is supported by the WISE research programme, which is financed by the Netherlands Organisation for Scientific Research (NWO). This work has been supported by the State Agency for Research of the Spanish MCIU through the ‘Centro de Excelencia Severo Ochoa’ award to the Instituto de Astrof´ısica de Andaluc´ıa (SEV-2017-0709). This research was supported by the Munich Institute for Astro- and Particle Physics (MIAPP) which is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)Peer reviewe

Mitocans induce lipid flip-flop and permeabilize the membrane to signal apoptosis

Pancratistatin (PST) and narciclasine (NRC) are natural therapeutic agents that exhibit specificity toward the mitochondria of cancerous cells and initiate apoptosis. Unlike traditional cancer therapeutic agents, PST and NRC are effective, targeted, and have limited adverse effects on neighboring healthy, noncancerous cells. Currently, the mechanistic pathway of action for PST and NRC remains elusive, which in part inhibits PST and NRC from becoming efficacious therapeutic alternatives. Herein, we use neutron and x-ray scattering in combination with calcein leakage assays to characterize the effects of PST, NRC, and tamoxifen (TAM) on a biomimetic model membrane. We report an increase in lipid flip-flop half-times (t1/2) (≈12.0%, ≈35.1%, and a decrease of ≈45.7%) with 2 mol percent PST, NRC, and TAM respectively. An increase in bilayer thickness (≈6.3%, ≈7.8%, and ≈7.8%) with 2 mol percent PST, NRC, and TAM, respectively, was also observed. Lastly, increases in membrane leakage (≈31.7%, ≈37.0%, and ≈34.4%) with 2 mol percent PST, NRC, and TAM, respectively, were seen. Considering the maintenance of an asymmetric lipid composition across the outer mitochondrial membrane (OMM) is crucial to eukaryotic cellular homeostasis and survival, our results suggest PST and NRC may play a role in disrupting the native distribution of lipids within the OMM. A possible mechanism of action for PST- and NRC-induced mitochondrial apoptosis is proposed via the redistribution of the native OMM lipid organization and through OMM permeabilization

Investigating the cut-off effect of n-alcohols on lipid movement: a biophysical study

Cellular membranes are responsible for absorbing the effects of external perturbants for the cell’s survival. Such perturbants include small ubiquitous molecules like n-alcohols which were observed to exhibit anesthetic capabilities, with this effect tapering off at a cut-off alcohol chain length. To explain this cut-off effect and complement prior biochemical studies, we investigated a series of nalcohols (with carbon lengths 2-18) and their impact on several bilayer properties, including lipid flip-flop, intervesicular exchange, diffusion, membrane bending rigidity and more. To this end, we employed an array of biophysical techniques such as time-resolved small angle neutron scattering (TRSANS), small angle X-ray scattering (SAXS), all atomistic and coarse-grained molecular dynamics (MD) simulations, and calcein leakage assays. At an alcohol concentration of 30 mol % of the overall lipid content, TR-SANS showed 1-hexanol (C6OH) increased transverse lipid diffusion, i.e. flip-flop. As alcohol chain length increased from C6 to C10 and longer, lipid flip-flop slowed by factors of 5.6 to 32.2. Intervesicular lipid exchange contrasted these results with only a slight cut-off at alcohol concentrations of 30 mol % but not 10 mol %. SAXS, MD simulations, and leakage assays revealed changes to key bilayer properties, such as bilayer thickness and fluidity, that correlate well with the effects on lipid flip-flop rates. Finally, we tie our results to a defect-mediated pathway for alcohol-induced lipid flip-flop

Vitamin e Does Not Disturb Polyunsaturated Fatty Acid Lipid Domains

The function of vitamin E in biomembranes remains a prominent topic of discussion. As its limitations as an antioxidant persist and novel functions are discovered, our understanding of the role of vitamin E becomes increasingly enigmatic. As a group of lipophilic molecules (tocopherols and tocotrienols), vitamin E has been shown to influence the properties of its host membrane, and a wealth of research has connected vitamin E to polyunsaturated fatty acid (PUFA) lipids. Here, we use contrast-matched small-angle neutron scattering and differential scanning calorimetry to integrate these fields by examining the influence of vitamin E on lipid domain stability in PUFA-based lipid mixtures. The influence of α-tocopherol, ?-tocopherol, and α-tocopherylquinone on the lateral organization of a 1:1 lipid mixture of saturated distearoylphosphatidylcholine (DSPC) and polyunsaturated palmitoyl-linoleoylphosphatidylcholine (PLiPC) with cholesterol provides a complement to our growing understanding of the influence of tocopherol on lipid phases. Characterization of domain melting suggests a slight depression in the transition temperature and a decrease in transition cooperativity. Tocopherol concentrations that are an order of magnitude higher than anticipated physiological concentrations (2 mol percent) do not significantly perturb lipid domains; however, addition of 10 mol percent is able to destabilize domains and promote lipid mixing. In contrast to this behavior, increasing concentrations of the oxidized product of α-tocopherol (α-tocopherylquinone) induces a proportional increase in domain stabilization. We speculate how the contrasting effect of the oxidized product may supplement the antioxidant response of vitamin E

Methanol Accelerates DMPC Flip-Flop and Transfer: A SANS Study on Lipid Dynamics

© 2019 Biophysical Society Methanol is a common solubilizing agent used to study transmembrane proteins/peptides in biological and synthetic membranes. Using small angle neutron scattering and a strategic contrast-matching scheme, we show that methanol has a major impact on lipid dynamics. Under increasing methanol concentrations, isotopically distinct 1,2-dimyristoyl-sn-glycero-3-phosphocholine large unilamellar vesicle populations exhibit increased mixing. Specifically, 1,2-dimyristoyl-sn-glycero-3-phosphocholine transfer and flip-flop kinetics display linear and exponential rate enhancements, respectively. Ultimately, methanol is capable of influencing the structure-function relationship associated with bilayer composition (e.g., lipid asymmetry). The use of methanol as a carrier solvent, despite better simulating some biological conditions (e.g., antimicrobial attack), can help misconstrue lipid scrambling as the action of proteins or peptides, when in actuality it is a combination of solvent and biological agent. As bilayer compositional stability is crucial to cell survival and protein reconstitution, these results highlight the importance of methanol, and solvents in general, in biomembrane and proteolipid studies

Time-resolved SANS reveals pore-forming peptides cause rapid lipid reorganization

Cells depend on proper lipid transport and their precise distribution for vital cellular function. Disruption of such lipid organization can be initiated by external agents to cause cell death. Here, we investigate two antimicrobial pore-forming peptides, alamethicin and melittin, and their influence on lipid intervesicular exchange and transverse lipid diffusion (i.e. flip-flop) in model lipid vesicles. Small angle neutron scattering (SANS) and a strategic contrast matching scheme show the mixing of two isotopically distinct dimyristoylphosphocholine (DMPC) vesicle populations is promoted upon the addition of high (1/40) and low (1/150, 1/1000) peptide-to-lipid (P/L) molar ratios. Parsing out the individual exchange and flip-flop rate constants revealed that alamethicin increases both DMPC flip-flop and exchange by ≈2-fold when compared to methanol alone (the carrier solvent of the peptides). On the other hand, melittin affected DMPC flip-flop by a factor of 1 to 4 depending on the concentration, but had little effect on inter-vesicle lipid exchange at low P/L ratios. Thermodynamic parameters measured at high protein concentrations (P/L = 1/40) yielded remarkable similarity in the values obtained for both peptides, indicating likeness in their mechanism of action on lipid motion despite differences in their proposed oligomeric pore structures. The entropic contributions to the free energy of activation became favorable upon peptide addition, while the enthalpy of activation remained the major barrier to lipid exchange and flip-flop. This journal i

Intercalative Stacking: A Critical Feature of DNA Charge-Transport Electrochemistry

In electrochemistry experiments on DNA-modified electrodes, features of the redox probe that determine efficient charge transport through DNA-modified surfaces have been explored using methylene blue (MB^+) and Ru(NH_3)_6^(3+) as DNA-binding redox probes. The electrochemistry of these molecules is studied as a function of ionic strength to determine the necessity of tight binding to DNA and the number of electrons involved in the redox reaction; on the DNA surface, MB^+ displays 2e^-/1H^+ electrochemistry (pH 7) and Ru(NH^3)_6^(3+) displays 1e^- electrochemistry. We examine also the effect of electrode surface passivation and the effect of the mode (intercalation or electrostatic) of MB^+ and Ru(NH_3)_6^(3+) binding to DNA to highlight the importance of intercalation for reduction by a DNA-mediated charge-transport pathway. Furthermore, in experiments in which MB^+ is covalently linked to the DNA through a σ-bonded tether and the ionic strength is varied, it is demonstrated that intercalative stacking rather than covalent σ-bonding is essential for efficient reduction of MB^+. The results presented here therefore establish that efficient charge transport to the DNA-binding moiety in DNA films requires intercalative stacking and is mediated by the DNA base pair array