Yukio Suezaki

A solid-solution theory of anesthetic interaction with lipid membranes: temperature span of the main phase transition

Anesthetics (or any other small additives) depress the temperature of the main phase transition of phospholipid bilayers. Certain anesthetics widen the temperature span of the transition, whereas others do not. The widening in a first-order phase transition is intriguing. In this report, the effects of additive molecules on the temperature and its span were explained by the solid-solution theory. By assuming coexistence of the liquid-crystal and solid-gel phases of lipid membranes at phase transition, the phase boundary is determined from the distribution of anesthetic molecules between the liquid-crystal membrane versus water and between the solid-gel membrane versus water. The theory shows that when the lipid concentration is large or when the lipid solubility of the drug is large, the width of the transition temperature increases, and vice versa. Highly lipid-soluble molecules, such as long-chain alkanols and volatile anesthetics, increase the width of the transition temperature when the lipid:water ratio is large, whereas highly water-soluble molecules, such as methanol and ethanol, do not. The aqueous phase serves as the reservoir for anesthetics. Depletion of the additive molecules from the aqueous phase is the cause of the widening. When the reservoir capacity is large, the temperature width does not increase. The theory also predicts asymmetry of the specific heat profile at the transition.

Response of bilayer phase transition temperature of acidic phospholipids to cationic surfactants

Abstract The effect of cationic surfactants on the bilayer phase transition of phospholipid vesicles was studied. Two types of acidic phospholipids, phosphatidic acid and phosphatidylglycerol, with different acyl chain length were examined. Cationic surfactants were alkyltrimethylammonium bromides with different alkyl chain length. The cationic surfactants with short chain length induced a monotonous decrease in the transition temperature, Tm, with increasing concentration, while those with long chain length exhibited a biphasic effect on Tm, i.e., increase in Tm at low concentrations and decrease in Tm at high concentrations. The surfactant chain length at which the biphasic effect on Tm appeared depended on the lipid acyl chain length; the longer lipid acyl chain needed the longer surfactant chain to bring about the biphasic effect. This behavior of the bilayer phase transition was common to acidic phospholipids regardless of the type of the lipid head groups. The complicated response of Tm to additives was explained by introducing interactions between the lipid and the surfactant in the membrane phase. According to this model, the behavior of Tm with respect to the additive concentration is determined by the combination of differences in the lipid-additive interaction energy and the free energy of additives between solid-gel and liquid-crystalline membranes.

Thermodynamic interrelation between the stability of black lipid membranes and bilayer vesicles in solution

Abstract The characteristics of the thermodynamic stable states of a black lipid membrane (BLM) and bilayer vesicles in solution and the thermodynamic interrelation between both systems are studied by theoretical extension of the study of BLM based on the adsorbed monolayer theory reported previously (Suezaki, Y., J. Theor. Biol. 71, 279 (1978)). Due to the strong intermolecular cohesive energy of lipids, the BLM can be in a stable state thermodynamically when the ratio of adsorbed lipids to dissolved lipids exceeds a certain amount. The free energy of bilayer vesicles is shown to be lower than that of the dissolved monomer lipids if the concentration of the total lipids exceeds the point at which the interfacial tension of the BLM diminishes to zero, provided that the solvent condition of both systems is the same. Thus, this paper clarifies the thermodynamic interrelation between the stability of BLMs and bilayer vesicles.

A statistical mechanical analysis of the effect of long-chain alcohols and high pressure upon the phase transition temperature of lipid bilayer membranes

Long-chain n-alcohols decrease the main phase-transition temperature of lipid vesicle membranes at low concentrations but increase it at high concentrations. The nonlinear phenomenon is unrelated to the interdigitation and is analyzed by assuming that alcohols form solid solutions with solid as well as liquid phases. The biphasic response originates from the balance of the free energy difference of alcohols in the liquid and solid membranes (delta gA) and the alcohol-lipid interaction free energy difference (delta u) between the two phases. When delta gA less than 0 and delta u greater than 0, or delta gA less than delta u less than 0, the transition temperature decreases monotonously according to the increase in the alcohol concentration. When delta gA greater than 0 and delta u less than 0, or delta gA greater than delta u greater than 0, it increases monotonously. Biphasic response occurs with a minimum temperature when delta u greater than delta gA greater than 0, and with a maximum temperature when delta u less than delta gA less than 0. When the alcohol carbon-chain length becomes closer to the lipid carbon-chain length, delta u is equalized by delta gA, and the temperature minimum of the main transition is shifted to extremely low alcohol concentrations. Hence, long-chain alcohols predominantly elevate the main transition temperature and lose their anesthetic potency. High pressure decreased both delta gA and delta u. Presumably, high pressure improves the packing efficiency of liquid membranes and decreases the difference between the solid and liquid membrane properties.

Cutoff effect of n-alkanols in an excitable model membrane composed of dioleyl phosphate

Abstract A series of n-alkanols from ethanol to tridecanol interacted with a negatively charged lipid membrane composed of dioleyl phosphate, which exhibited a

Effect of local anesthetics on the electrical characteristics of an excitable model membrane composed of dioleyl phosphate. I, Static and steady-state response

The local anesthetics, tetracaine, procaine and lidocaine, interacted with a negatively charged lipid membrane composed of dioleyl phosphate (DOPH), which exhibited a self-sustained oscillation of the membrane potential. The anesthetics depolarized the membrane potential when present in increasing concentrations, whereas they increased the membrane resistance at low concentrations and decreased it at high concentrations. The above results were analyzed on the basis of electrochemical theory taking into account ion flux across the membrane. The electrical characteristics are affected by both the hydrophobicity and the diffusion constant of local anesthetics within the membrane.

Effect of local anesthetics on the electrical characteristics of an excitable model membrane composed of dioleyl phosphate II. Dynamic response.

The effects of local anesthetics (tetracaine, procaine and lidocaine) on self-sustained electrical oscillations were studied for a lipid membrane comprising dioleyl phosphate (DOPH). This model membrane exhibits oscillation of the membrane potential in a manner similar to that of nerve membranes, i.e., repetitive firing, in the presence of an ion-concentration gradient, on the application of d.c. electric current. Relatively weak anesthetics such as procaine and lidocaine increased the frequency of self-sustained oscillation, and finally induced aperiodic, rapid oscillation. The strong anesthetic tetracaine inhibited oscillation.

A Study of the Electronic Properties of Organic Semiconductors

The conduction mechanism of the crystals of tetracyanoquinodimethan (TCNQ) anion radical salts is studied. Unpaired π-electrons in TCNQ - anions are described by the Hubbard model with a narrow band and one electron per molecular site. The electronic spectra of the Hubbard model are determined by the Hubbards third solution. The value of the electrical conductivity of TEA(TCNQ) 2 at 23°C agrees with experimental values quantitatively.

A statistical mechanical theory for the adsorption of protein to liposomal membranes.

The observed topology change of spherical lipid vesicles to coffee cups [Saitoh, A. et al., Proc. Natl. Acad. Sci. USA 95 (1998) 1026] was analyzed by a statistical mechanical theory. The topology change was due to the adsorption of talin molecules to the orifices of the coffee cups. The adsorption isotherm of talin between an aqueous solution and the vesicle membrane was analyzed by taking account of the bending energy of the membrane. The equilibrium is determined by the balance of the energy gain for the adsorption of talin to the periphery of the vesicles and the change of the bending energy of the membrane due to the shape change. The observed coexistence of coffee cups and sheet-like vesicles were reproduced. Vesicles with two orifices were also analyzed and theoretically reproduced.

Effect of inhalation anesthetics on swimming activity of artemia salina

The swimming movement of artemia salina in the artificial sea water was measured by using the video camera system in the absence and the presence of anesthetics, i.e. enfiurane, halothane, and isofiurane. The movement of artemia looked random at a glance but the obtained distribution curve for the swimming speed was skewed toward the high speed side somewhat resembling a Maxwellian distribution curve seen in the statistics of ideal gases. When anesthetics were added, the distribution curve became sharpened and shifted to the low speed side, which is similar to a behavior of ideal gasses when they are cooled down. The mean swimming-speed was decreased eventually leading to an irreversible death with increasing the anesthetic dose. The activity was analyzed by using the hydrodynamic equation. The ED50, which is a dose that causes a 50% reduction in the activity, of all anesthetics used in this study was quite similar to the MAC values for human. It was also suggested that an interaction between anesthetics and artemia was highly cooperative since the large Hill coefficients were obtained for all three anesthetics used.