Interactions of Monovalent and Divalent Cations with Cardiolipin Monolayers

Cardiolipin is a mitochondrial phospholipid with four alkyl chains and two phosphate moieties. Tetramyristoyl cardiolipin (TMCL, (14:0)₄CL) monolayers at the air-water interface are characterized by compression isotherms, which show a liquid expanded/liquid condensed phase transition. The phase transition surface pressure π_c depends on the composition of the aqueous solution. In a calculation, this is attributed to the electrostatic double layer, which is induced by the head groups of the model membrane, and competitive ion binding. The intrinsic binding constant is large for protons ( K_H = 10 L/mol) and small for monovalent cations ( K_M (Na⁺, K⁺, Cs⁺) = 10^-3 L/mol). The different intrinsic binding constants explain the non-monotonic behavior of π_c on increasing the salt concentration: raising the monovalent salt concentration increases π_c by charging the TMCL monolayer until 0.1 mol/L, then screening effects dominate and decrease π_c by reducing the electrostatic repulsion between lipid head groups. When at fixed 0.15 mol/L NaCl concentration, the concentration of divalent cations is increased, π_c decreases. The intrinsic binding constants of divalent cations follow the sequence Sr²⁺ < Mg²⁺ < Mn²⁺ ≈ Zn²⁺ ≈ Ca²⁺ ( K_D,Ca = 1.2 L/mol). The predictive power of the calculations was tested with different solutions.