An osmotic model for the fusion of biological membranes

A molecular model for fusion-fission reactions in membranes is proposed that is based on data from studies on artificially induced cell fusion and on the behaviour of phospholipid bilayers: it is put forward as a framework for further investigations into this fundamental property of biological systems.     

Lateral organization of biological membranes

The lateral organization of biological membranes is of great importance in many biological processes, both for the formation of specific structures such as super-complexes and for function as observed in signal transduction systems. Over the last years, AFM studies, particularly of bacterial photosynthetic membranes, have revealed that certain proteins are able to segregate into functional domains with a specific organization. Furthermore, the extended non-random nature of the organization has been suggested to be important for the energy and redox transport properties of these specialized membranes. In the work reported here, using a coarse-grained Monte Carlo approach, we have investigated the nature of interaction potentials able to drive the formation and segregation of specialized membrane domains from the rest of the membrane and furthermore how the internal organization of the segregated domains can be modulated by the interaction potentials. These simulations show that long-range interactions are necessary to allow formation of membrane domains of realistic structure. We suggest that such possibly non-specific interactions may be of great importance in the lateral organization of biological membranes in general and in photosynthetic systems in particular. Finally, we consider the possible molecular origins of such interactions and suggest a fundamental role for lipid-mediated interactions in driving the formation of specialized photosynthetic membrane domains. We call these lipid-mediated interactions a ‘lipophobic effect.’     

The organization of biological membranes

A nomenclature for the organization of biological membranes is proposed. The terms primary (composition), secondary (transverse and lateral distribution), tertiary (membrane stacking/unstacking), and quaternary (membrane-membrane, cell-cell interactions) levels of organization are used by analogy with protein structure, but at each level the membrane organization is more complex and dynamic than protein structure.     

Detailed molecular dynamics simulations of model biological membranes containing cholesterol

Detailed molecular dynamics simulations performed to study the nature of lipid raft domains that appear in model membranes are reviewed in this paper. The described simulations were performed on hydrated bilayers containing binary mixtures of cholesterol with phospholipids and also on ternary mixtures containing cholesterol, a phospholipid with a high main transition temperature T_m, and a phospholipid with a low transition temperature T_m. These simulations provide qualitative and semi-quantitative information about cholesterol-lipid interactions and also a testing ground for major assumptions made to explain the nature of lipid rafts in model membranes.     

The molecular organization of nerve membranes

Summary Plasma membranes were isolated from two types of squid nerves which have morphologically, different ratios of axolemma/Schwannlemma (A/S). These membranes were studied by means of differential and density gradient centrifugation.Thoroughly dissected giant axons were used as membrane source having low A/S ratio. Retinal fibers were used as membrane source with high A/S ratio. A similar procedure for the isolation of the plasma membranes was used for both types of squid axons.Differential centrifugation showed that at 1,500×g, the yield of membrane enzymes (Na, K-ATPase and NADH-ferricyanide oxidoreductase) from giant axon homogenates was 2 to 5 times greater than from retinal nerve homogenates, but at 105,000×g the opposite was the case, the yield from retinal axons being about two times greater. Thus, the major part of the membrane material from the retinal nerve seems to be less dense than the membrane material from giant axons.The behavior of the 105,000×g fraction from both types of fibers was studied by determining protein Na, K-ATPase, and NADH-oxidoreductase along a lineal sucrose gradient (10 to 40%; centrifuged at 40,600×g for 90 min). By any of the three measurements, retinal axons yielded a greater amount (2:1) of plasma membranes sedimenting at low sucrose concentration (16 to 25%) as compared to that observed at high sucrose concentration (35 to 38%). Giant axons, on the contrary, yielded a higher proportion of membranes (2.5:1) sedimenting at high sucrose concentrations (over 40%).The experimental data indicate that a different cellular origin can account for the behavior of nerve membranes along lineal gradient centrifugation. The membranes floating at low sucrose concentration (light membranes) can be tentatively ascribed to the axolemma; the membranes found at high sucrose concentration (heavy membranes) to the Schwannlemma and basement membranes.In accord with their high A/S morphological ratio, squid retinal axons yielded 5 times more light membranes (axolemma) than dissected giant axons.     

An elementary kinetic model of energy coupling in biological membranes

The purpose of this work is to contribute to the understanding of the fundamental kinetic properties of the processes of energy coupling in biological membranes. For this, we consider a model of a microorganism that, in its plasma membrane, expresses two electrogenic enzymes (E(1) and E(2)) transporting the same monovalent cation C and electrodiffusive paths for C and for a monovalent anion A. E(1) (E(2)) couples transport C to the reaction S(1)<-->P(1) (S(2)<-->P(2)). We developed a mathematical model that describes the rate of change of the electrical potential difference across the membrane, of the internal concentrations of C and A, and of the concentrations of S(2) and P(2). The enzymes are incorporated via two-state kinetic models; the passive ionic fluxes are represented by classical formulations of electrodiffusion. The microorganism volume is maintained constant by accessory regulatory devices. The model is utilized for stationary and dynamic studies for the case of bacteria employing the electrochemical gradient of Na(+) as energetic intermediate. Among other conclusions, the results show that the membrane potential represents the relevant kinetic intermediate for the overall coupling between the energy donor reaction S(1)<-->P(1) and the synthesis of S(2).     

Exceptional molecular organization of canthaxanthin in lipid membranes

Canthaxanthin (β,β-carotene 4,4' dione) used widely as a drug or as a food and cosmetic colorant may have some undesirable effects on human health, caused mainly by the formation of crystals in the macula lutea membranes of the retina of an eye. Experiments show the exceptional molecular organization of canthaxanthin and a strong effect of this pigment on the physical properties of lipid membranes. The most striking difference between canthaxanthin and other macular pigments is that the effects of canthaxanthin at a molecular level are observed at much lower concentration of this pigment with respect to lipid (as low as 0.05 mol%). An analysis of the molecular interactions of canthaxanthin showed molecular mechanisms such as: strong van der Waals interactions between the canthaxanthin molecule and the acyl chains of lipids, restrictions to the segmental molecular motion of lipid molecules, modifications of the surface of the lipid membranes, effect on the membrane thermotropic properties and finally interactions based on the formation of the hydrogen bonds. Such interactions can lead to a destabilization of the membrane and loss of membrane compactness. In the case of the retinal vasculature, it can lead to an increase in the permeability of the retinal capillary walls and the development of retinopathy.     

Sphingomyelin-cholesterol interactions in biological and model membranes

Cholesterol and sphingomyelin are both important plasma membrane constituents in cells. It is now becoming evident that these two lipid classes affect each other's metabolism in the cell to an extent that was not previously appreciated. It is the aim of this review to present recent data in the literature concerning both molecular and membrane properties of the two lipid classes, how they interact in membranes (both biological and model), and the consequences their mutual interaction have on different functional and metabolic processes in cells and lipoproteins.     

Stochastic model of domain kinetics in biological membranes

A stochastic storage model based on the behavior of macroscopic variables of the system is used to describe the kinetics of raft-like domains in biological membranes. For a simple output model, we examine the features of the system behavior corresponding to the noise-induced nonequilibrium phase transitions. Characteristics of the behavior of the statistical system are obtained: an explicit form of the stationary distribution of the number of domains; ratios for the phase transition points; the expression for the first two moments of the random domain concentration, and the expression for the lifetime of membrane domains in the stationary state.     

Relay model of lipid peroxidation in biological membranes

The present study examines the evidence for the important role of free radicals, localized on carbon atoms of the hydrocarbon chains, in lipid peroxidation. These radicals show a great inter- and intramolecular mobility in membranes by the way of relay-transfer (isomerisation). The sequence of intermediate steps of shift of free radicals in membranes with correction for molecular organization of the hydrocarbon zone of membranes, the intramembrane localization of unsaturated links and the gradient of mobility of the hydrocarbon chains are described. The effect of inhibitors in lipid peroxidation are interpreted in terms of decay of hydrocarbon free radicals as a result of its interaction with the antioxidant molecules. The natural antioxidants having a side chain (such as tocopherols) may be regarded as a some kind of "channel" through which free radicals leave the hydrocarbon moiety of the membrane. The processes of lipid peroxidation in membranes are subjected to a great extent to the requirements of the theory of oxidation of solid polymers and hydrocarbons.     

A model for phase transitions in lipid bilayers and biological membranes

We wish to present an order-disorder model for the observed phase transitions in lipid bilayers and biological membranes. We show that the model may, under certain circumstances, exhibit two phase transitions, one corresponding to positional disordering of entire lipid molecules, and the other corresponding to orientational disordering in the hydrocarbon chains. We then give results of our numerical analysis of the model and compare them with experimental data. Shortcomings of the model and future directions for analyses of this type are also discussed.     

Cholesterol modulates maculosin's orientation in model systems of biological membranes. Relevance towards putative molecular recognition

Fluorescence techniques were used to study (1) the extent of insertion of the bioactive cyclic dipeptide cyclo(l-tyrosyl-l-prolyl), maculosin, in model systems of membranes of 1, 2-palmitoyl-sn-glycero-3-phosphatidyl choline (DPPC) or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyl choline (POPC), (2) its in-depth location in those lipidic membranes, and (3) the influence of cholesterol on the dipeptides's location and orientation. Partition into lipidic bilayers is extensive, mainly for liquid crystalline phase membranes (K(p)=1.3x10(4)). Maculosin locates at the lipid head groups level regardless of the membrane system. Nevertheless, its orientation is lipid phase dependent. When maculosin was inserted in liquid crystalline phase bilayers, its phenolic ring was perpendicular to the membrane surface, whereas it changed orientation when inserted in gel phase membranes. Cholesterol was able to reverse the lipid phase influence on maculosin's orientation.     

Application of 31P-NMR saturation transfer techniques to investigate phospholipid motion and organization in model and biological membranes

The potential of ³¹P-NMR saturation transfer experiments for determining motional characteristics (in the millisecond to second time scale) of phospholipids in model and biological membranes is demonstrated. A technique to separate membrane phospholipid ³¹P-NMR signals from those of small water-soluble phosphates in intact cells in liver tissue is also illustrated.