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Enhancement in Lipid Bilayer Partitioning of Lysolipids and Fatty Acids Induced by their Composition

Distribution of the solutes: lysopalmitoylphosphatidylcholine (LPPC), Palmitic acid (PA) and their 1:1 mixtures between water and dipalmitoylphosphatidylcholine (DPPC) bilayer were determined using a fluorescence probe that selectively detects these solutes in water. Membrane phase as well as solute concentration itself affects partitioning. Water solute concentrations were obtained at each of several bilayer lipid concentrations between 10 and 400 μM, from slopes of the linear variation of probe fluorescence properties with total solute concentrations of up to 10 % of the solvent lipid concentration. Dynamic Light Scattering experiments confirmed that the lipid/solute aggregates were vesicles in this range. Lipid concentration dependence of the solute component in water was fit to a thermodynamic model of solute distribution between two coexisting solvents. Water/bilayer partition coefficient and the solute transfer free energy were determined from the fit. Main findings are: (1) Water to bilayer transfer free energy of solute is lower for 0 to 2 % solute mole fraction than for 2 to 10 %, signaling composition induced bilayer relaxation that increases bilayer solubility, beginning at 2 % solute mole fraction. (2) Partition coefficients are in the order LPPC>PA> LPPC+PA at 37 °C. The enhanced partition coefficient of LPPC+PA signifies synergism toward increased solubility in the bilayer-gel phase. Enhancement effects were not present, where the DPPC bilayer is in the liquid phase, The observed order in the partition coefficients, at 50 °C, was LPPC≈LPPC+PA>PA. The behavior of the partition coefficients in the gel and liquid phase is similar in character to the observed presence of synergism in the transmembrane permeabilityin the bilayer gel phase and lack of it in the liquid phase. The present results provide experimental evidence that increased presence of solutes in the membrane also enhance transmembrane permeability.

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