Softening of lipid bilayers

The softening of wet lipid bilayer membranes during their gel-to-fluid first-order phase transition is studied by computer simulation of a family of two-dimensional microscopic interaction models. The models include a variable number, q, of lipid chain conformational states, where 2q10. Results are presented as functions of q and temperature for a number of bulk properties, such as internal energy, specific heat, and lateral compressibility. A quantitative account is given of the statistics of the lipid clusters which are found to form in the neighborhood of the transition. The occurrence of these clusters is related to the softening and the strong thermal density fluctuations which dominate the specific heat and the lateral compressibility for the high-q models. The cluster distributions and the fluctuations behave in a manner reminiscent of critical phenomena and percolation. The findings of long-lived metastable states and extremely slow relaxational behavior in the transition region are shown to be caused by the presence of intermediate lipid chain conformational states which kinetically stabilize the cluster distribution and the effective phase coexistence. This has as its macroscopic consequence that the first-order transition apperas as a continuous transition, as invariably observed in all experiments on uncharged lecithin bilayer membranes. The results also suggest an explanation of the non-horizontal isotherms of lipid monolayers. Possible implications of lipid bilayer softening and enhanced passive permeability for the functioning of biological membranes are discussed.Abbreviations PC phosphatidvlcholine - DMPC dimyristoyl PC - DPPC dipalmitoyl PC - ac alternating current - DSC differential scanning calorimetry - T _m lipid gel-to-fluid phase transition temperature - TEMPO 2,2,6,6-tetramethylpiperidine-N-oxyl Supported by the Danish Natural Science Research Council and A/S De Danske Spritfabrikkers JubilæumslegatSupported in part by the NSERC of Canada and Le FCAC du Quebec     

Studies on the lack of cooperativity in the melting of lipid bilayers

The gel-to-fluid first-order melting transition of lipid bilayers is simulated by the use of a microscopic interaction model which includes a variable number of lipid-chain conformational states. The results suggest that the experimental observation of ‘continuous melting’ in pure wet lipid bilayers, rather than being ascribed to the presence of impurities, may be explained as a result of kinetically caused metastability of intermediate lipid-chain conformations.     

The computer as a laboratory for the physical chemistry of membranes

A mini-review is given of some recent advances in the use of computer-simulation approaches to the study of physico-chemical properties of lipid bilayers and biological membranes. The simulations are based on microscopic molecular interaction models as well as random-surface models of fluid membranes. Particular emphasis is put on those properties that are controlled by the many-particle character of the lamellar membrane, i.e. correlations and fluctuations in density, composition and large-scale conformational structure. It is discussed how dynamic membrane heterogeneity arises and how it is affected by various molecular species interacting with membranes, such as cholesterol, drugs, insecticides, as well as polypeptides and integral membrane proteins. The influence of bending rigidity and osmotic-pressure gradients on large-scale membrane conformation and topology is described.     

Phase separation dynamics and lateral organization of two-component lipid membranes.

The non-equilibrium dynamic ordering process of coexisting phases has been studied for two-component lipid bilayers composed of saturated di-acyl phospholipids with different acyl chain lengths, such as DC14PC-DC18PC and DC12PC-DC18PC. By means of a microscopic interaction model and computer-simulation techniques the non-equilibrium properties of these two mixtures have been determined with particular attention paid to the effects of the non-equilibrium ordering process on membrane heterogeneity in terms of local and global lateral membrane organization. The results reveal that a sudden temperature change that takes the lipid mixture from the fluid one-phase region into the gel-fluid phase-coexistence region leads to the formation of a large number of small lipid domains which slowly are growing in time. The growth of the lipid domains, which is limited by long-range diffusion of the lipid molecules within the two-dimensional membrane plane, gives rise to the existence of a highly heterogeneous percolative-like structure with a network of interfacial regions that have properties different from those of the phase-separated gel and fluid bulk phases. The results, which are discussed in relation to recent experimental observations interpreted in terms of a percolative-like membrane structure within the two phase region (Almeida, P.F.F., Vaz, W.L.C., and T.E. Thompson. 1992. Biochemistry 31:7198-7210), suggest that non-equilibrium effects may influence lipid domain formation and membrane organization on various length and time scales. Such effects might be of importance in relation to membrane processes that require molecular mobility of the membrane components in restricted geometrical environments of the compartmentalized lipid membrane.     

The permeability and the effect of acyl-chain length for phospholipid bilayers containing cholesterol: theory and experiment.

The model of Cruzeiro-Hansson et al. (Biochim. Biophys. Acta (1989) 979, 166-1176) for lipid-cholesterol bilayers at low cholesterol concentrations is used to predict the thermodynamic properties and the passive ion permeability of lipid bilayers as a function of acyl-chain length and cholesterol concentration. Numerical simulations based on the Monte Carlo method are used to determine the equilibrium state of the system near the main gel-fluid phase transition. The permeability is calculated using an ansatz which relates the passive permeability to the amount of interfaces formed in the bilayer when cholesterol is present. The model predicts at low cholesterol contents an increase in the membrane permeability in the transition region both for increasing cholesterol concentration and for decreasing chain length at a given value of the reduced temperature. This is in contrast to the case of lipid bilayers containing high cholesterol concentrations where the cholesterol strongly suppresses the permeability. Experimental results for the Na+ permeability of C15PC and DPPC (C16PC) bilayers containing cholesterol are presented which confirm the theoretical predictions at low cholesterol concentrations.     

A general model for the interaction of foreign molecules with lipid membranes: drugs and anaesthetics

A general microscopic interaction model is proposed to describe the changes in the physical properties of phospholipid bilayer membranes due to foreign molecules which, to different degrees, partition between the membrane phases and the aqueous environment. The model is a multi-state lattice model for the main phase transition of lipid bilayers and the foreign molecules are assumed to intercalate as interstitials in the lattice. By varying the model parameters, the diversity in the thermodynamic properties of the model is explored using computer-simulation techniques which faithfully take account of the thermal fluctuations. The calculations are performed in both the canonical and the grand canonical ensembles corresponding to the cases where the concentration of foreign molecules in the membrane is either fixed or varies as the external conditions are changed. A classification of the diverse thermal behaviour, specifically with regard to the phase diagram, the specific heat, the density fluctuations, and the partition coefficient, is suggested with a view to rationalizing a large body of experimental measurements of the effects of different foreign molecules on membrane properties. The range of foreign molecules considered includes compounds as diverse as volatile general anaesthetics like halothane, cocaine-derived local anaesthetics like procaine, calcium-channel blocking drugs like verapamil, antidepressants like chlorpromazine, and anti-cancer agents like adriamycin.     

Resource tracking in marine parasites: going with the flow?

Understanding how diversity interacts with energy supply is of broad ecological interest. Most studies to date have investigated patterns within trophic levels, reflecting a lack of food webs which include information on energy flow. We added parasites to a published marine energy‐flow food web, to explore whether parasite diversity is correlated with energy flow to host taxa. Parasite diversity was high with 36 parasite taxa affecting 40 of the 51 animal taxa. Adding parasites increased the number of trophic links per species, trophic link strength, connectance, and food chain lengths. There was evidence of an asymptotic relationship between energy flowing through a food chain and parasite diversity, although there were clear outliers. High parasite diversity was associated with host taxa which were highly connected within the food web. This suggests that energy flow through a taxon may favour parasite diversity, up to a maximal value. The evolutionary and energetic basis for that limitation is of key interest in understanding the basis for parasite diversity in natural food webs and thus their role in food web dynamics.     

Parasites as prey in aquatic food webs: implications for predator infection and parasite transmission

While the recent inclusion of parasites into food‐web studies has highlighted the role of parasites as consumers, there is accumulating evidence that parasites can also serve as prey for predators. Here we investigated empirical patterns of predation on parasites and their relationships with parasite transmission in eight topological food webs representing marine and freshwater ecosystems. Within each food web, we examined links in the typical predator–prey sub web as well as the predator–parasite sub web, i.e. the quadrant of the food web indicating which predators eat parasites. Most predator– parasite links represented ‘concomitant predation’ (consumption and death of a parasite along with the prey/host; 58–72%), followed by ‘trophic transmission’ (predator feeds on infected prey and becomes infected; 8–32%) and predation on free‐living parasite life‐cycle stages (4–30%). Parasite life‐cycle stages had, on average, between 4.2 and 14.2 predators. Among the food webs, as predator richness increased, the number of links exploited by trophically transmitted parasites increased at about the same rate as did the number of links where these stages serve as prey. On the whole, our analyses suggest that predation on parasites has important consequences for both predators and parasites, and food web structure. Because our analysis is solely based on topological webs, determining the strength of these interactions is a promising avenue for future research.