The calculation of heat capacity curves and phase diagrams based on regular solution theory

The intermolecular interactions of molecules within the bilayer are responsible for the lipid organisation, e.g. domain formation, and the interaction and stabilisation of proteins within the lipid matrix. The mixing behaviour of lipids, which reflects the intrinsic molecular interactions, can be deduced from the shape of the phase diagram (temperature vs. mole fraction diagram), which is constructed from the analysis of heat capacity curves obtained by DSC. However, there are no objective procedures to determine the temperatures corresponding to the border lines of the coexistence region, i.e. the liquidus and solidus curves of the phase diagram. The main challenge to overcome is to develop an objective method for the correct determination of the onset and offset temperatures of the melting curve for every single transition curve in a standardized manner. The presented paper describes a procedure for the simulation of heat capacity curves. In a second step, based on the results from the heat capacity curve simulation, a phase diagram is calculated using a non-ideal, non-symmetric mixing model. The non-ideality parameters obtained from the calculation describe the intermolecular interaction of both components in a single phase region. Using this procedure, examples of the mixing behaviour of various binary phospholipid systems are analysed and it is shown how the mixing behaviour is influenced by external factors like e.g. the pH or ionic strength.