Phase behavior and permeability properties of phospholipid bilayers containing a short-chain phospholipid permeability enhancer

The thermodynamic phase behavior and trans-bilayer permeability properties of multilamellar phospholipid vesicles containing a short-chain DC10PC phospholipid permeability enhancer have been studied by means of differential scanning calorimetry and fluorescence spectroscopy. The calorimetric scans of DC14PC lipid bilayer vesicles incorporated with high concentrations of DC10PC demonstrate a distinct influence on the lipid bilayer thermodynamics manifested as a pronounced freezing-point depression and a narrow phase coexistence region. Increasing amounts of DC10PC lead to a progressive lowering of the melting enthalpy, implying a mixing behavior of the DC10PC in the bilayer matrix similar to that of a substitutional impurity. The phase behavior of the DC10PC–DC14PC mixture is supported by fluorescence polarization measurements which, furthermore, in the low-temperature gel phase reveal a non-monotonic concentration-dependent influence on the structural bilayer properties; small concentrations of DC10PC induce a disordering of the acyl chains, whereas higher concentrations lead to an ordering. Irreversible fluorescence quench measurements demonstrate a substantial increase in the trans-bilayer permeability over broad temperature and composition ranges. At temperatures corresponding to the peak positions of the heat capacity, a maximum in the trans-bilayer permeability is observed. The influence of DC10PC on the lipid bilayer thermodynamics and the associated permeability properties is discussed in terms of microscopic effects on the lateral lipid organization and heterogeneity of the bilayer.