A Universal Correlation Predicts Permeability Coefficients of Fluid- and Gel-Phase Phospholipid and Phospholipid-Cholesterol Bilayers for Arbitrary Solutes

The permeability of gel-phase phospholipids is typically about an order of magnitude lower than that of the same compositions in the fluid phase, yet a quantitative description of the ordering factors leading to this difference has been elusive. The present analysis examines these factors with particular focus on the area per phospholipid chain, Ac, and its relationship to the minimum area per molecule in the crystalline state, A0. It is shown that fluid- and gel-phase phospholipid permeabilities can be reconciled by postulating a minimum area per chain Ac,0 = 17.1 Å2, substantially less than one would estimate by dividing the accepted value A0 = 40.8 Å2 by 2. An extended data set of phospholipid and phospholipid-cholesterol bilayer permeability data extending over 9 orders of magnitude is analyzed and correlated according to the developed relationship (N = 85, s = 0.3024, r2 = 0.9332). Individual permeability values are consequently predicted to within an average deviation of 100.3024 or about a factor of 2. The analysis is broadly applicable in the fluid phase but is restricted to gel-phase phospholipid compositions that do not contain cholesterol. Guidance for the latter scenario is provided.