Relationship between fluidity and ionic permeability of bilayers from natural mixtures of phospholipids

Proton and calcium permeability coefficients of large unilamellar vesicles made from natural complex mixtures of phospholipids were measured in various conditions and related to membrane fluidity. Permeability coefficients at neutral pH and 25 degrees C were in the range of 10(-4) cm sec-1 and 2.5 X 10(-11) cm sec-1 for protons and calcium, respectively. With the exception of two cases, (H+) greater than 10(-4) M and (Ca2+) greater than 10(-3) M, fluidity increases correspond to permeability increases. Theoretical analysis shows that, for both ions, the measured values of permeability coefficients imply that the permeation process is controlled by the product D1D2 of the diffusion coefficient from the medium into the membrane (D1) by the diffusion coefficient in the membrane (D2). Further analysis of D1 values deduced from combined use of permeability and fluidity data shows that the solubilization should occur in a medium of dielectric constant of about 12, suggesting the involvement of the hydration water of membranes. High proton concentrations, although having virtually no effect on fluidity, trigger the appearance of lateral heterogeneity in membranes, as seen by 31P NMR, and large permeability increases. It is proposed that the main effect of fluidity and/or lateral heterogeneity on permeability may be via the membrane hydration control. We conclude that the current assumption that permeability is controlled by fluidity should be regarded with caution, at least in the case of ions and natural mixtures of phospholipids.