Carboxylic acid or primary amine titration at the lipid-water interface: on the role of electric charges and phospholipid acyl chain composition. A spin labeling experiment

Abstract

The dissociation equilibrium pH of a stearic acid spin probe and of the primary amine group of cysteamine was evaluated in the phospholipidic matrix of model membranes in gel phase (L β) and in liquid-crystalline phase (L α). This study shows that the apparent p K a or p K b values depend on: (i) the thermodynamic phase of the lipidic bilayers; (ii) the nature of the lipidic components including either the polar head region (choline, serine moieties or exogenous electric charge-carrying cholesteryl esters) or the hydrophobic core (different phospholipid acyl chain length); (iii) the nature of the ionizable group, Δp K bilayer − p K water) of carboxylic acid or primary amine groups being opposite respectively ( Δp K a = + 2.5 for stearic acid and Δp K b = − 4.9 for cysteamine, in DPPC in fluid phase). An interpretation of this p K shifting is given by an interaction model of the ionizable molecule with the phospholipid bilayer, showing that Δp K can be modulated by two parameters: the partition coefficient ratio of both the non-ionized and the ionized forms ( K H / K) of the interacting molecule and the surface charge density (Ψ 1) at the lipid/water interface: