PERMEABILITY OF ACETIC-ACID ACROSS GEL AND LIQUID-CRYSTALLINE LIPID BILAYERS CONFORMS TO FREE-SURFACE-AREA THEORY

Solubility-diffusion theory, which treats the lipid bilayer membrane a s a bulk lipid solvent into which permeants must partition and diffuse across, fails to account for the effects of lipid bilayer chain order on the permeability coefficient of any given permeant. This study add resses the scaling factor that must be applied to predictions from sol ubility-diffusion theory to correct for chain ordering. The effects of bilayer chemical composition, temperature, and phase structure on the permeability coefficient (P-m) of acetic acid were investigated in la rge unilamellar vesicles by a combined method of NMR line broadening a nd dynamic light scattering. Permeability values were obtained in dist earoylphosphatidylcholine, dipalmitoylphosphatidylcholine, dimyristoyl phosphatidylcholine, and dilauroylphosphatidylcholine bilayers, and th eir mixtures with cholesterol, at various temperatures both above and below the gel-->liquid-crystalline phase transition temperatures (T-m) . A new scaling factor, the permeability decrement f, is introduced to account for the decrease in permeability coefficient from that predic ted by solubility-diffusion theory owing to chain ordering in lipid bi layers. Values of f were obtained by division of the observed P-m by t he permeability coefficient predicted from a bulk solubility-diffusion model. In liquid-crystalline phases, a strong correlation (r=0.94) be tween f and the normalized surface density sigma was obtained: In f=5. 3-10.6 sigma. Activation energies (E(a)) for the permeability of aceti c acid decreased with decreasing phospholipid chain length and correla ted with the sensitivity of chain ordering to temperature, partial der ivative sigma/partial derivative(1/T), as chain length was varied. P-m values decreased abruptly at temperatures below the main phase transi tion temperatures in pure dipalmitoylphosphatidylcholine and dimyristo ylphosphatidylcholine bilayers (30-60-fold) and below the pretransitio n in dipalmitoylphosphatidylcholine bilayers (8-fold), and the linear relationship between In f and sigma established for liquid-crystalline bilayers was no longer followed. However, in both gel and liquid-crys talline phases In f was found to exhibit an inverse correlation with f ree surface area (In f=-0.31-29.1/a(f), where a(f) is the average free area (in square angstroms) per lipid molecule). Thus, the lipid bilay er permeability of acetic acid can be predicted from the relevant chai n-packing properties in the bilayer (free surface area), regardless of whether chain ordering is varied by changes in temperature, lipid cha in length, cholesterol concentration, or bilayer phase structure, prov ided that temperature effects on permeant dehydration and diffusion an d the chain-length effects on bilayer barrier thickness are properly t aken into account.