DPPC/cholesterol Revisited: Interaction Models to Explain the Excess Heat Capacity in Unilamellar Vesicles

Abstract

The binary lipid system DPPC/cholesterol has been studied since the 1970s. Strangely enough, the nature of the interaction between the phospholipid and cholesterol remains unclear. Also strangely enough, for decades, the thermodynamics of these binary mixture have been investigated mainly in multilamellar vesicles (MLVs). More recently, giant unilamellar vesicles (GUVs) have been used, which are excellent to study lipid phase separation, especially by fluorescence confocal microscopy, but do not easily lend themselves to calorimetry. However, the heat capacity of DPPC across the main phase transition is similar in GUVs and in large unilamellar vesicles (LUVs) but quite different from that in MLVs. Much of the attention in the thermodynamics of the phase transition in DPPC/cholesterol has been concerned with understanding the heat capacity in MLVs. Here we turn our attention to the DPPC/cholesterol binary system in LUVs, which we think is a much more relevant type of vesicle to understand the molecular interactions between DPPC and cholesterol. We compare the experimental heat capacity (melting) curves in LUVs with the results of Monte Carlo calculations using various models of the interaction between these lipids, including complex formation and simple pairwise interactions. This work has been supported by NSF grant CHE-1464769.