Mechanism of intermembrane phosphatidylcholine transfer: effects of pH and membrane configuration

The mechanism of phospholipid transfer between membranes has been studied as a function of the configuration and concentration of donor and recipient membranes. The study was motivated by the observation that dimyristoylphosphatidylcholine transfers from sonicated vesicles to erythrocytes at a 4-fold faster rate at pH 5.5 than at pH 7.4. It is unexpected that the solubility of phosphatidylcholine should be affected by pH changes in this range; indeed, the more hydrophilic homolog dilauroylphosphatidylcholine transfers at closely similar rates at pH 5.5 and 7.4. The behavior of the more hydrophobic lipid is not consistent with transfer solely as a monomer passing through the aqueous phase. The effects of membrane proximity on phospholipid transfer were examined in dilution experiments employing intact erythrocytes, resealed ghosts, erythrocyte membrane buds, and sonicated vesicles as both donor and recipient membranes. For both hydrophobic and less hydrophobic lipids, the kinetics of intermembrane transfer were affected significantly by dilution at constant donor:recipient ratios. The results were fit to a kinetic model containing contributions from both through-solution monomer transfer and transient collisional transfer. The model predicts that the mechanism of intermembrane transfer varies with experimental conditions such as membrane concentration, donor and acceptor membrane area, and surface curvature. Through-solution monomer transfer predominates for less hydrophobic lipids at all values of pH and membrane concentration, and for more hydrophobic lipids at very high membrane dilutions. Transient collisional transfer contributes significantly to the rate for relatively hydrophobic lipids in concentrated donor-acceptor systems, an effect that is particularly evident at pH values below 6. The size and surface configuration of donor and recipient membranes also alter the relative contributions of through-solution and collisional transfer.