Kinetics of the interactions of a dicarboxylic porphyrin with unilamellar lipidic vesicles: interplay between bilayer thickness and pH in rate control.

The transfer of a dicarboxylic porphyrin from phosphatidylcholine fluid-phase unilamellar vesicles towards albumin is studied focusing on bilayer thickness and pH effects. The kinetics of this process yield the rate constants for the porphyrin flip-flop from the inner to the outer hemileaflet and its exit towards aqueous medium. Phospholipids with monounsaturated 14-22 carbon chains are used. Interplay between bilayer thickness and pH for the control of the rate constants is observed. This results in the amplification, at physiological pH, of the effect of membrane thickness on the flip-flop and exit rates as compared to pH 8.5 and 6.5. These data are explained by the degree of porphyrin burying within the bilayer resulting from a compromise between favorable hydrophobic interactions with the hydrocarbon phase and unfavorable penetration of the polar carboxylic chains. The balance between the two effects depends particularly on the neutralization of one carboxylic chain. Considering the bilayer hydrophobicity profile and the porphyrin size, the optimization of hydrophobic interactions appears dependent on the bilayer thickness. The flip-flop and the exit are governed by neutralization and deprotonation of the carboxylic chains, respectively, the rate of these proton exchanges being dependent on the porphyrin location within the bilayer.