Diffusion-controlled generation of a proton-motive force across a biomembrane

Respiration in bacteria involves a sequence of energetically-coupled electron and proton transfers creating an electrochemical gradient of protons (a proton-motive force) across the inner bacterial membrane. With a simple kinetic model we analyze a redox loop mechanism of proton-motive force generation mediated by a molecular shuttle diffusing inside the membrane. This model, which includes six electron-binding and two proton-binding sites, reflects the main features of nitrate respiration in E. coli bacteria. We describe the time evolution of the proton translocation process. We find that the electron-proton electrostatic coupling on the shuttle plays a significant role in the process of energy conversion between electron and proton components. We determine the conditions where the redox loop mechanism is able to translocate protons against the transmembrane voltage gradient above 200 mV with a thermodynamic efficiency of about 37%, in the physiologically important range of temperatures from 250 to 350 K.Comment: 26 pages, 4 figures. A similar model is used in arXiv:0806.3233 for a different biological system. Minor changes in the Acknowledgements sectio

Phase Behaviour of Amphiphilic Monolayers: Theory and Simulation

Coarse grained models of monolayers of amphiphiles (Langmuir monolayers) have been studied theoretically and by computer simulations. We discuss some of the insights obtained with this approach, and present new simulation results which show that idealised models can successfully reproduce essential aspects of the generic phase behaviour of Langmuir monolayers.Comment: To appear in J. Phys.: Cond. Matte

Proton Wires in an Electric Field: the Impact of Grotthuss Mechanism on Charge Translocation

We present the results of the modeling of proton translocation in finite H-bonded chains in the framework of two-stage proton transport model. We explore the influence of reorientation motion of protons, as well as the effect of electric field and proton correlations on system dynamics. An increase of the reorientation energy results in the transition of proton charge from the surrounding to the inner water molecules in the chain. Proton migration along the chain in an external electric field has a step-like character, proceeding with the occurrence of electric field threshold-type effects and drastic redistribution of proton charge. Electric field applied to correlated chains induces first a formation of ordered dipole structures for lower field strength, and than, with a further field strength increase, a stabilization of states with Bjerrum D-defects. We analyze the main factors responsible for the formation/annihilation of Bjerrum defects showing the strong influence of the complex interplay between reorientation energy, electric field and temperature in the dynamics of proton wire.Comment: 28 pages, 9 figure

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

The influence of anesthetics, neurotransmitters and antibiotics on the relaxation processes in lipid membranes

In the proximity of melting transitions of artificial and biological membranes fluctuations in enthalpy, area, volume and concentration are enhanced. This results in domain formation, changes of the elastic constants, changes in permeability and slowing down of relaxation processes. In this study we used pressure perturbation calorimetry to investigate the relaxation time scale after a jump into the melting transition regime of artificial lipid membranes. This time corresponds to the characteristic rate of domain growth. The studies were performed on single-component large unilamellar and multilamellar vesicle systems with and without the addition of small molecules such as general anesthetics, neurotransmitters and antibiotics. These drugs interact with membranes and affect melting points and profiles. In all systems we found that heat capacity and relaxation times are related to each other in a simple manner. The maximum relaxation time depends on the cooperativity of the heat capacity profile and decreases with a broadening of the transition. For this reason the influence of a drug on the time scale of domain formation processes can be understood on the basis of their influence on the heat capacity profile. This allows estimations of the time scale of domain formation processes in biological membranes.Comment: 12 pages, 6 figure

Changes in Phospholipid Composition Studied by HPLC and Electric Properties of Liver Cell Membrane of Ethanol-Poisoned Rats

Ethanol introduced into the organism undergoes rapid metabolism to acetaldehyde and then to acetic acid. The process is accompanied by formation of reactive oxygen species (ROS), which damage mainly lipids of membrane cells. The effects of ROS can be neutralized by administering preparations with antioxidant properties. The natural preparations of this kind are teas

Stabilization of tilt order by chain flexibility in Langmuir monolayers

Langmuir monolayers are modeled as systems of short chains, which are confined to a planar surface at one end, but free to move within the plane. The phase behavior is calculated in a mean field approximation, which combines the self consistent field method with elements of classical density functional theory. It is shown that phases with tilt order are unstable in systems of stiff chains, but can be stabilized by chain conformational entropy in systems of sufficiently flexible chains. The chain entropy is also responsible for the appearance of an additional untilted phase, the liquid expanded phase. The region of stability of the different phases is discussed, and their microscopic structure is analyzed in some detail.Comment: to appear in Phys. Rev.

In Vitro Surfactant Structure-Toxicity Relationships: Implications for Surfactant Use in Sexually Transmitted Infection Prophylaxis and Contraception

Background The need for woman-controlled, cheap, safe, effective, easy-to-use and easy-to-store topical applications for prophylaxis against sexually transmitted infections (STIs) makes surfactant-containing formulations an interesting option that requires a more fundamental knowledge concerning surfactant toxicology and structure-activity relationships. Methodology/Principal Findings We report in vitro effects of surfactant concentration, exposure time and structure on the viability of mammalian cell types typically encountered in the vagina, namely, fully polarized and confluent epithelial cells, confluent but non-polarized epithelial-like cells, dendritic cells, and human sperm. Representatives of the different families of commercially available surfactants – nonionic (Triton X-100 and monolaurin), zwitterionic (DDPS), anionic (SDS), and cationic (CnTAB (n = 10 to 16), C12PB, and C12BZK) – were examined. Triton X-100, monolaurin, DDPS and SDS were toxic to all cell types at concentrations around their critical micelle concentration (CMC) suggesting a non-selective mode of action involving cell membrane destabilization and/or destruction. All cationic surfactants were toxic at concentrations far below their CMC and showed significant differences in their toxicity toward polarized as compared with non-polarized cells. Their toxicity was also dependent on the chemical nature of the polar head group. Our results suggest an intracellular locus of action for cationic surfactants and show that their structure-activity relationships could be profitably exploited for STI prophylaxis in vaginal gel formulations. The therapeutic indices comparing polarized epithelial cell toxicity to sperm toxicity for all surfactants examined, except C12PB and C12BZK, does not justify their use as contraceptive agents. C12PB and C12BZK are shown to have a narrow therapeutic index recommending caution in their use in contraceptive formulations. Conclusions/Significance Our results contribute to understanding the mechanisms involved in surfactant toxicity, have a predictive value with regard to their safety, and may be used to design more effective and less harmful surfactants for use in topical applications for STI prophylaxis.Foundation for Science and Technology of the Portuguese Ministry of Science and Higher Educatio