DI-n-propylsulfoxide (DPSO) effect on the thermal transitions of liposomes.

DPSO affects noticeably the water structure, acting as cryoprotector if present at low concentrations. On the contrary, at higher concentrations, its toxic effect prevails and acts as a destroyer of cellular membrane structure. To explain this behaviour and correlate it with the hydrophobic/hydrophilic properties of DPSO, we studied the hydrated multilamellar liposomes of both dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) in the presence of increasing amounts of DPSO by means of Differential Scanning Calorimetry (DSC). DPSO/water mixtures were prepared by direct mixing of both component, with the χDPSO ranging from 0.00 up to 0.20. Liposomes were prepared by mixing the lipids with the DPSO/water mixtures up to a final lipid concentration of about 20 % w/w; DSC scans were performed by a Mettler-Toledo DSC 821e calorimeter at a heating rate of 2.0°C/min. At the lower DPSO concentrations, the pretransition disappeared and the main transition temperature (Tm) decreased. Fig. 1 shows that the effect on Tm appeared to be more marked in the DMPC liposomes than in DPPC ones. This behaviour suggests the existence of strong hydrophobic interactions involving the n-propyl chains and the ability of DPSO molecules to insert, at least partially, into the hydrophobic core of the lipid bilayer. Nevertheless, even the polar interactions due to the S=O groups play a role. Indeed, Tm values increased at the higher DPSO contents, in particular in the DPSO/DPPC system, indicating that the bilayer rigidifies as a consequence of the H2O replacement by DPSO molecules. The importance of the hydrophobic interactions is further confirmed by the ΔH behaviour, as it is observed from fig. 2. In fact, in both systems an increase in ΔH was initially observed as well as a ΔH decrease at higher DPSO concentrations, but in the case of DMPC liposomes the ΔH value decreased up to become zero when χDPSO is 0.2. Also the length of the hydrophobic lipidic chains plays a role. In fact, the bilayer structure is conserved in the DPPC liposomes at all DPSO concentrations, analogously to that reported for DMSO1. On the contrary, in the DMPC liposomes the bilayer structure appears to be fully disrupted when the DPSO/H2O ratio overcomes 40 % w/w (concentration at which the cryoprotective effect of both DMSO and DESO reaches its maximum). The observe behaviour suggest that DPSO alone can be used as a cryoprotector only if it is present at low concentration.