NEW APPROACHES TO THE SIMULATION OF HEAT-CAPACITY CURVES AND PHASE-DIAGRAMS OF PSEUDOBINARY PHOSPHOLIPID MIXTURES

A simulation program using least-squares minimization was developed to calculate and fit heat capacity (cp) curves to experimental thermogra ms of dilute aqueous dispersions of phospholipid mixtures determined b y high-sensitivity differential scanning calorimetry. We analyzed cp c urves and phase diagrams of the pseudobinary aqueous lipid systems ol/ 1,2-dipalmitoyl-sn-glycero-3phosphatidylcholine (DMPG/DPPC) and 1,2-di myristoyl-sn-glycero-3-phosphatidic d/1,2-dipalmitoyl-sn-glycero-3-pho sphatidylcholine (DMPA/DPPC) at pH 7. The simulation of the cp curves is based on regular solution theory using two nonideality parameters r ho(g) and rho(l) for symmetric nonideal mixing in the gel and the liqu id-crystalline phases. The broadening of the cp curves owing to limite d cooperativity is incorporated into the simulation by convolution of the cp curves calculated for infinite cooperativity with a broadening function derived from a simple two-state transition model with the coo perative unit size n = Delta(vH)/Delta H-cal as an adjustable paramete r. The nonideality parameters and the cooperative unit size turn out t o be functions of composition. In a second step, phase diagrams were c alculated and fitted to the experimental data by use of regular soluti on theory with four different model assumptions. The best fits were ob tained with a four-parameter model based on nonsymmetric, nonideal mix ing in both phases. The simulations of the phase diagrams show that th e absolute Values of the nonideality parameters can be changed in a ce rtain range without large effects on the shape of the phase diagram as long as the difference of the nonideality parameters for rho(g) for t he gel and rho(l) for the liquid-crystalline phase remains constant. T he miscibility in DMPG/DPPC and DMPA/DPPC mixtures differs remarkably because, for DMPG/DPPC, Delta(rho) = rho(l) - rho(g) is negative, wher eas for DMPA/DPPC this difference is positive. For DMPA/DPPC, this dif ference is interpreted as being caused by a negative rho(g) value, ind icating complex formation of unlike molecules in the gel phase.