Molecular-level pictures of the phase transitions of saturated and unsaturated phospholipid binary mixtures

Abstract

Binary lipid mixtures consisting of saturated and unsaturated lipids are important models for natural cell membranes. However, a detailed molecular picture for the phase transition process of such lipid binary mixtures remains unclear. Herein, by using deuterated dipalmitoylphosphatidylcholine (DPPC-d₆₂) and hydrogenated dioleoylphosphatidic acid (DOPA), we expect to separately analyze the changes of the two lipid components during thermotropic phase transitions by temperature-dependent Fourier transform infrared (FTIR) spectroscopy, and uncover the hidden secrets of a seemingly single endothermic peak observed in differential scanning calorimetry (DSC) experiments. We found that at low DOPA concentrations (10–20 mol%), a gel to fluid conformational transition of DPPC-d₆₂ and a fluidization transition of DOPA by DPPC-d₆₂ were observed. The two lipids were found to have nonsynchronous conformational rearrangements in the tail regions upon thermotropic phase transitions, with the change of DOPA earlier than DPPC-d₆₂. Besides, in the mixed fluid phase at 40 °C, the unsaturated DOPA can be fluidized (loosened) by the saturated DPPC-d₆₂, and such an isothermal fluidization effect is more pronounced at elevated DPPC-d₆₂ concentrations. At higher DOPA contents (30–50 mol%), only DPPC-d₆₂ molecules have conformational transitions upon heating. The present work demonstrates for the first time that the unsaturated lipid component can have significant conformational reorganizations in the phase transition process of a saturated–unsaturated binary lipid mixture.