Time evolution of the thermotropic behavior of spontaneous liposomes and disks of the DMPC–DTAC aqueous system

In this work, solubilization of the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) by the cationic detergent n-dodecyltrimethylammonium chloride (DTAC) was studied in aqueous solution, at a fixed DMPC concentration and variable detergent:lipid (D:L) molar ratios. The colloidal nanostructures present in different stages of the solubilization process were characterized using micro-differential scanning calorimetry (DSC) and dynamic light scattering (DLS) techniques. For total (analytical) D:L molar ratios below ≈1, DTAC monomers incorporate into the DMPC liposome bilayers, forming smaller and more fluid vesicles than pure DMPC liposomes. At D:L ≈ 1–2, vesicles begin to rupture, coexisting with intact vesicles and bilayer fragments. At D:L ≈ 2–12.5, discoidal and spherical micelles are formed and coexist with vesicles; a slow structural rearrangement of the system, monitored in successive DSC heating/cooling cycles, was observed, and is reported for the first time. Finally, for D:L above ≈15–20, the bilayers are completely dissolved, and the main aggregates in solution become spherical micelles, which slowly evolve to cylindrical (threadlike) micelles. Based on the dependence of the temperature and enthalpy of transitions on the total D:L molar ratio, at constant DMPC concentration, a schematic model, showing the different colloidal nanostructures present in the solubilization process, is proposed.

Graphical abstractTime evolution of DSC heating thermograms show the slow structural rearrangement of unilamellar vesicles and disks of the DTAC–DMPC aqueous system, in a mixture with a DTAC:DMPC molar ratio of 2.Figure optionsDownload full-size imageDownload high-quality image (88 K)Download as PowerPoint slideResearch highlights► DMPC–DTAC vesicle bilayers are more fluid than those of pure DMPC liposomes. ► Flat disks of DMPC–DTAC have the most rigid bilayers. ► DMPC–DTAC vesicles are smaller than pure DMPC liposomes; both are bigger than disks. ► Coexistent DMPC–DTAC vesicles and disks show a slow structural rearrangement. ► DTAC–DMPC spherical micelles slowly evolve to cylindrical (threadlike) micelles.