EXCHANGE AND FLIP-FLOP OF DIMYRISTOYLPHOSPHATIDYLCHOLINE IN LIQUID-CRYSTALLINE, GEL, AND 2-COMPONENT, 2-PHASE LARGE UNILAMELLAR VESICLES

The rate and extent of spontaneous exchange of dimyristoylphosphatidylcholine (DMPC) from large unilamellar vesicles (LUV) composed of either DMPC or mixtures of DMPC/distearoyl-phosphatidylcholine (DSPC) have been examined under equilibrium conditions. The phase state of the vesicles ranged from all-liquid-crystalline through mixed gel/liquid-crystalline to all-gel. The exchange rate of DMPC between liquid-crystalline DMPC LUV, measured between 25 and 55 °C, was found to have an Arrhenius activation energy of 24.9 ± 1.4 kcal/mol. This activation energy and the exchange rates are very similar to those obtained for the exchange of DMPC between DMPC small unilamellar vesicles (SUV). The extent of exchange of DMPC in LUV was found to be approximately 90%. This is in direct contrast to the situation in DMPC SUV where only the lipid in the outer monolayer is available for exchange. Thus, transbilayer movement (flip-flop) is substantially faster in liquid-crystalline DMPC LUV than in SUV. Desorption from gel-phase LUV has a much lower rate than gel-phase SUV with an activation energy of 31.7 ± 3.7 kcal/mol compared to 11.5 ± 2 kcal/mol reported for SUV. A defect-mediated exchange in gel-phase SUV, which is not the major pathway for exchange in LUV, is proposed on the basis of the thermodynamic parameters of the activation process. Surprisingly, the rates of DMPC exchange between DMPC/DSPC two-component LUV, measured over a wide range of compositions and temperatures, were found to exhibit very little dependence on the composition or phase configuration of the vesicles. Evidence is given for defect-mediated exchange from two-component gel phases. The fraction of DMPC exchanging between two-component vesicles indicated fast flip-flop relative to exchange at many, but not all, compositions and temperatures at or above 28 mol % DMPC. Although DMPC exchange between LUV composed of 0.1 mol % DMPC in DSPC has desorption rates equal to those at the other compositions, the flip-flop rates at this composition are at least an order of magnitude smaller. © 1990, American Chemical Society. All rights reserved.