2 MECHANISMS OF PERMEATION OF SMALL NEUTRAL MOLECULES AND HYDRATED IONS ACROSS PHOSPHOLIPID-BILAYERS

The Gibbs free energy of dipole or ion permeation of lipid bilayers is calculated as the sum of all electrostatic, solvophobic and specific interactions. Partitioning models are consistent with dipole permeatio n and some features of ionic permeation, particularly if the solvophob ic energy is taken into account. Ionic and dipole permeabilities are e xtremely sensitive to the ionic/dipolar radius. Despite this sensitivi ty, calculations of the permeability can be carried out for typical mo novalent cations, and provide reasonable estimates, but only for hydra ted species. An alternative mechanism proposed for ionic permeation in volves the occurrence of transient pore-like defects in lipid bilayers which permit ions to bypass the Born energy barrier. The two alternat ive hypotheses, partitioning vs. transient pores, can be tested by mea suring the ionic and dipolar permeation through bilayers of varying th ickness. Experimental observations for both potassium and proton perme ability are consistent with the transient pore mechanism for shorter c hain lipids, but tend towards the theoretical line for partitioning mo dels for longer chain lipids. Results for small neutral solutes are be st explained by the solubility-diffusion mechanism. The proposed metho d of calculation of the Gibbs free energy of ion or dipole membrane tr ansfer and the liquid membrane permittivity can be effectively used no t only in describing the biophysical properties of membranes, but also in extraction processes, pharmaceutical applications and liquid membr ane separations. (C) 1997 Elsevier Science S.A.