Examination of the thermotropic behavior of aqueous dispersions of dipalmitoylphosphatidylcholine-cholesterol mixtures by high-sensitivity scanning calorimetry has revealed that the phospholipid gel to liquid-crystalline phase transition consists of two components. One, a relatively sharp transition centered at 39.6-40.7 degrees C, exhibits a transition enthalpy change which decreases linearly with increasing cholesterol content, approaching zero at a cholesterol content of about 25 mol %. The other, a broad, lower intensity transition centered at approximately 41.5 degrees C for cholesterol concentrations of 20 mol %, displays an enthalpy change which is maximal at about 20-25 mol % cholesterol and which decreases as the cholesterol content decreases to zero or increases above 25 mol %. The origin of these two transitions is discussed in terms of a separation of these lipid mixtures into cholesterol-rich and cholesterol-poor domains.

A recently developed differential scanning calorimeter has been used to characterize the thermotropic behavior of aqueous dispersions of liposomes containing sphingomyelin. Liposomes derived from sheep brain sphingomyelin exhibit a broad gel-liquid crystalline phase transition in the temperature range of 20-45 degrees C. The transition is characterized by maxima in the heat capacity function at 31.2 and 37.1 degrees C and a total enthalpy change of 7.2 +/-0.4 kcal/mol. Beef brain sphingomyelin liposomes behave similarly but exhibit heat capacity maxima at 30, 32, and 38 degrees C and a total enthalpy change of 6.9 kcal/mol. The thermotropic behavior of four pure synthetic sphingomyelins is reminiscent of multilamellar lecithin liposomes in that a single, sharp, main transition is observed. Results obtained for liposomes containing mixtures of different sphingomyelins are complex. A colyophilized mixture of N-palmitoylsphingosinephosphorylcholine, N-stearoylsphingosinephosphorylcholine, and N-lignocerylsphingosinephosphorylcholine in a 1 : 1 : 1 mol ratio exhibits a single transition with a Tm below that observed for the individual components. On the other hand a 1 : 1 mixture of N-stearoylsphingosinephosphorylcholine and 1-palmitoyl-2-oleylphosphatidylcholine exhibits three maxima in the heat capacity function. It is clear from these results that the thermotropic behavior of sphingomyelin-containing liposomes is a complex function of the exact composition. Furthermore, it appears that the behavior of the liposomes derived from natural sphingomyelins cannot be explained in terms of phase separation of the individual components.

The effects of gaseous anesthetics and pressure on the thermotropic behavior of multilamellar dipalmitoylphosphatidylcholine liposomes were studied by using a highsensitivity differential scanning calorimeter. It was found that halothane and enflurane decreased the transition temperature and increased the width of the transition without affecting the enthalpy change for the main gel-to-liquid crystalline transition. This emonstrated that the anesthetics decreased the degree of cooperative interaction between phospholipid molecules within the bilayer. Increasing the pressure increased the transition temperature but did not affect the transition width or enthalpy change. However, the increase in pressure reversed the effect of anesthetic on both the transition temperature and transition width. It is sugested that an understanding of the effect of anesthetics on the degree of cooperative interaction between phospholipids may be a key to understanding anesthetic action.The physiological effect of inhalation anesthetics is likely a manifestation of the perturbation of membrane functions associated with synaptic transmission of nerve impulses. This conclusion is primarily based on the high degree of correlation between anesthetic potency and lipid solubility (1, 2). Although it is possible that the primary sites of the action of anesthetics are specific membrane proteins, an attractive alternative is that such action is the result of induced changes in the dynamic structure of the lipid matrix.Trudell and coworkers (3) have demonstrated that general anesthetics decrease the gel-to-liquid crystalline phase transition temperature of phospholipid bilayers and that this effect can be reversed by application of moderate pressures [-100 atmospheres (atm) (10 MPa)] to the system. This result is particularly intriguing because the physiological effect can also be reversed by moderate pressures (4). Recently, Trudell (5) developed a phenomenological theory of anesthesia based on the concept of lateral phase separation in the membrane. This theory focuses on the absolute increase in fluidity of the phospholipid matrix caused by anesthetics. It was suggested that, when phase separation no longer exists, membranes are less able to facilitate the protein conformational changes necessary for normal physiological function.In order to assess carefully the effect of the gaseous anesthetics on the thermotropic behavior of lipid bilayers, a detailed study was initiated using a highly sensitive differential scanning calorimeter. In addition, the influence of pressure on this behavior was ascertained by using a pressure cell adapted for this calorimeter. The results of this study show that the general anesthetics halothane (CF3CHBrCl) and enflurane (CHF2OCF2CHFCI) decrease the transition temperature without affecting the enthalpy change for the transition but that the degree of cooperative interaction between phospholipid molecules is decreased. Both these effects can be reversed by the application of moderate pressures. We there...

The thermotropic behavior of aqueous dispersions of palmitoylsphingomyelin-cholesterol and lignoceryl-sphingomyelin-cholesterol mixtures has been examined by high-sensitivity differential scanning calorimetry. When less than 25 mol % cholesterol is mixed with either sphingomyelin, the calorimetric endotherm is composed of a sharp and a broad component. The sharp-component enthalpy change decreases as the mole percent cholesterol increases with the extrapolated zero enthalpy point being 25 to 30 mol %. With palmitoylsphingomyelin, the temperature of maximum heat capacity of the sharp component decreases monotonically with increasing cholesterol content, while the lignocerylsphingomyelin sharp-component maximum remains constant until more than 20 mol % sterol is present. The broad-component enthalpy change maximizes at 3--4 kcal/mol between 10 and 20 mol % cholesterol and decreases as the ratio of cholesterol is increased or decreased from this range for both sphingomyelins. The results are compared with those from a previous study on dipalmitoylphosphatidylcholine-cholesterol mixtures and are interpreted as evidence for the coexistence of cholesterol-rich and cholesterol-poor phases.

Students in an upper-level thermal physics course were asked to compare quantities related to the First Law of Thermodynamics along with similar mathematical questions devoid of all physical context. We report on a comparison of student responses to physics questions involving interpretation of ideal gas processes on P-V diagrams and to analogous mathematical qualitative questions about the signs of and comparisons between the magnitudes of various integrals. Student performance on individual questions combined with performance on the paired questions shows evidence of isolated understanding of physics and mathematics. Some difficulties are addressed by instruction.