Structure of symmetric and asymmetric "ripple" phases in lipid bilayers

We reproduce the symmetric and asymmetric ``rippled'' $P_{\beta'}$ states of lipid membranes by Monte Carlo simulations of a coarse-grained molecular model for lipid-solvent mixtures. The structure and properties compare favorably with experiments. The asymmetric ripple state is characterized by a periodic array of fully interdigitated ``defect'' lines. The symmetric ripple state maintains a bilayer structure, but is otherwise structurally similar. The formation of both ripple states is driven by the propensity of lipid molecules with large head groups to exhibit splay.Comment: 4 pages, 4 figure

Long-term self-reported attendance in exercise training or lung choir and status of quality of life following initial pulmonary rehabilitation for COPD

Background: Both adherence rates to pulmonary rehabilitation (PR) programmes and long-term attendance in exercise training after PR remain a challenge. In our previous randomised controlled trial (RCT), effects were positively associated with a dose-response pattern, regardless of whether PR contained conventional physical exercise training (PExT) or Singing for Lung Health (SLH) as a training modality within a 10 weeks’ PR programme for chronic obstructive pulmonary disease (COPD). However, long-term status of this RCT cohort remains unknown. In this study, we investigated whether current status (=attendance in supervised exercise training or a lung choir and scoring in quality of life (QoL)) was related to initial PR completion, randomisation, or adherence. Methods: We collected data via telephone, using a researcher-developed questionnaire on current self-reported attendance in supervised exercise training or a lung choir and on perceived benefits of the initial RCT intervention. Additionally, we used COPD-validated questionnaires (primarily: QoL (measure: St George's Respiratory Questionnaire; SGRQ). Results: In 2023 (i.e., mean/median 4.7 years after initial PR), surviving participants were contacted (n = 196; 73% of 270), and 160 (82% of 196) were included. Out of the included participants, 30 (19%) had not completed initial PR. Compared to the initial PR-completers, non-completers reported less current attendance in exercise training or lung choir (24% vs. 46%, p = 0.03) but SGRQ scores were comparable. Yet, those who attended exercise training or lung choir at present (n = 66/160; 41% out of 160) reported better QoL score than those with no current attendance (SGRQ; Attending: 39.9 ± 15.4; Not attending: 43.1 ± 16.7; p = 0.02). Neither having had SLH instead of PExT, nor adherence level during initial PR, was related to current attendance or to QoL scores. Conclusion: This study indicates that long-term self-reported attendance and current QoL scores are positively related to initial completion of a PR programme. Surprisingly, neither initial PR content (PExT or SLH) nor initial PR adherence was related to long-term outcomes. We suggest that future PR programmes include special attention to those who do not complete PR to support long-term attendance and QoL status

VII Scandinavian Copd Research Symposium, Holmenkollen, Oslo 18th-19th November 2016

Peer reviewe

Self-Assembly in Monoelaidin Aqueous Dispersions: Direct Vesicles to Cubosomes Transition

Background: In the present study, synchrotron small-angle X-ray scattering (SAXS) and Cryo-TEM were used to characterize the temperature-induced structural transitions of monoelaidin (ME) aqueous dispersion in the presence of the polymeric stabilizer F127. We prove that the direct transition from vesicles to cubosomes by heating this dispersion is possible. The obtained results were compared with the fully hydrated bulk ME phase. Methodology/principal findings: Our results indicate the formation of ME dispersion, which is less stable than that based on the congener monoolein (MO). In addition, the temperature-dependence behavior significantly differs from the fully hydrated bulk phase. SAXS findings indicate a direct L(alpha)-V(2) internal transition in the dispersion. While the transition temperature is conserved in the dispersion, the formed cubosomes with internal Im3m symmetry clearly contain more water and this ordered interior is retained over a wider temperature range as compared to its fully hydrated bulk system. At 25 degrees C, Cryo-TEM observations reveal the formation of most likely closely packed onion-like vesicles. Above the lamellar to non-lamellar phase transition at 65 degrees C, flattened cubosomes with an internal nanostructure are observed. However, they have only arbitrary shapes and thus, their morphology is significantly different from that of the well-shaped analogous MO cubosome and hexosome particles. Conclusions/significance: Our study reveals a direct liposomes-cubosomes transition in ME dispersion. The obtained results suggest that the polymeric stabilizer F127 especially plays a significant role in the membrane fusion processes. F127 incorporates in considerable amount into the internal nanostructure and leads to the formation of a highly swollen Im3m phase

Sheddable Coatings for Long-Circulating Nanoparticles

Nanoparticles, such as liposomes, polymeric micelles, lipoplexes and polyplexes are frequently studied as targeted drug carrier systems. The ability of these particles to circulate in the bloodstream for a prolonged period of time is often a prerequisite for successful targeted delivery. To achieve this, hydrophilic ‘stealth’ polymers, such as poly(ethylene glycol) (PEG), are used as coating materials. Such polymers shield the particle surface and thereby reduce opsonization by blood proteins and uptake by macrophages of the mononuclear phagocyte system. Yet, after localizing in the pathological site, nanoparticles should deliver their contents in an efficient manner to achieve a sufficient therapeutic response. The polymer coating, however, may hinder drug release and target cell interaction and can therefore be an obstacle in the realization of the therapeutic response. Attempts have been made to enhance the therapeutic efficacy of sterically stabilized nanoparticles by means of shedding, i.e. a loss of the coating after arrival at the target site. Such an ‘unmasking’ process may facilitate drug release and/or target cell interaction processes. This review presents an overview of the literature regarding different shedding strategies that have been investigated for the preparation of sterically stabilized nanoparticulates. Detach mechanisms and stimuli that have been used are described

The multiple faces of self-assembled lipidic systems

Lipids, the building blocks of cells, common to every living organisms, have the propensity to self-assemble into well-defined structures over short and long-range spatial scales. The driving forces have their roots mainly in the hydrophobic effect and electrostatic interactions. Membranes in lamellar phase are ubiquitous in cellular compartments and can phase-separate upon mixing lipids in different liquid-crystalline states. Hexagonal phases and especially cubic phases can be synthesized and observed in vivo as well. Membrane often closes up into a vesicle whose shape is determined by the interplay of curvature, area difference elasticity and line tension energies, and can adopt the form of a sphere, a tube, a prolate, a starfish and many more. Complexes made of lipids and polyelectrolytes or inorganic materials exhibit a rich diversity of structural morphologies due to additional interactions which become increasingly hard to track without the aid of suitable computer models. From the plasma membrane of archaebacteria to gene delivery, self-assembled lipidic systems have left their mark in cell biology and nanobiotechnology; however, the underlying physics is yet to be fully unraveled

Freeze-thaw effects on lipid-bilayer vesicles investigated by differential scanning calorimetry

AbstractDifferential scanning calorimetry (DSC) has been used to study the effects of repeated freezing and thawing on dipalmitoylphosphatidylcholine (DPPC) vesicles. Aqueous suspensions of both multilamellar vesicles (MLVs) and large unilamellar vesicles (LUVs) were cycled between −37 and 8 °C, and for each thawing event, the enthalpy of ice-melting was measured. In the case of MLVs, the enthalpy increased each time the vesicles were thawed until a steady state was attained. In contrast, the enthalpies measured for LUV suspensions were independent of the number of previous thawing events. It was concluded that MLVs in terms of freezing characteristics contain two pools of water, namely bulk water and interlamellar water. Interlamellar water does not freeze under the conditions employed in the present study, and the MLVs therefore experience freeze-induced dehydration, which is the reason for the observed increase in ice-melting enthalpy. Furthermore, the thermodynamic results suggest that the osmotic stress resulting from the freeze-induced dehydration changes the lamellarity of the MLVs