Calorimetric properties of mixtures of ganglioside GM1 and dipalmitoylphosphatidylcholine.

High sensitivity differential scanning calorimetry has been employed to study the thermotropic behavior, over the range from 12-83”C, of dispersed mixtures of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) with bovine brain ganglioside GM1 of high purity. No thermal phase transitions of pure GM1 alone in excess water could be detected, even at concentrations of 4 mg/ml? over the temperature range of these studies. The excess heat capacity curve for multilamellar dis- persions of pure DPPC was as previously reported, with a pretransition at 32.7”C and a main transition at 41.4”C. As GM1 was added in increasing amounts to DPPC, the curve remained qualitatively similar up to a GM1 mole fraction (xc) of 0.24, but the temperature of the pretransition gradually increased, from 32.7 to about 37”C, and that of the main transition gradually increased, from 41.4-44.3%. When xo was increased above 0.24, several changes were observed: 1) the tur- bidity of the suspensions abruptly decreased, becoming negligible at xo r, 0.40; 2) the pretransition disap- peared; 3) the amplitude of the main transition began to decrease; and 4) a new transition appeared at a higher temperature, 48°C. The calculated enthalpy of the main transition was constant, within the error of the measurement, up to xo = 0.24, and then decreased linearly to zero over the range of xo between 0.24 and 0.63; over the same range the enthalpy of the transition at 48°C increased linearly from zero, so that the sum of the two enthalpies remained constant. All the observed thermotropic transitions were experimentally reversi- ble over a period of at least 2 weeks. These results are interpreted in terms of a model, consistent with pre- vious observations, in which GM1 at concentrations up to xG = 0.24 is incorporated into the multilamellar DPPC structure, but at higher concentrations induces the progressive formation of mixed micelles because of the repulsive interaction of its bulky and negatively charged head groups. In both lamellar and micellar structures, GM1 appears to stabilize the phospholipid lattice, causing the transition temperature to be higher than for pure DPPC. The thermotropic behavior of biomembranes and their lipid components has come increasingly under investigation (1, 2). The calorimetric properties of the numerically predominant