A comment on the water permeability through planar lipid bilayers

Dear Sir: In a recent article, Finkelstein (1976) has shown that the measured water permeabil i ty th rough a leci thin-decane planar bilayer m em b ran e is similar to the calculated permeabili ty t h rou g h a sheet o f n h e x a d e c a n e 50 ,~ thick. Th a t is, the measured water permeabil i ty, Pa, was found equal to DKhc/AX, where D is the diffusion constant o f water in water, Khe is the waterm-hexadecane part i t ion coefficient, and AX is the thickness o f the hydrocarbon "membrane . " We suggest that there are a n u m b e r o f internal factors in the above calculation that may compensate for one ano the r so as to give ag reement with exper iment . At the hear t o f the problem is the question: can the inter ior o f the bilayer be t reated as an isotropic, three-dimensional liquid? T h e r e is mount ing evidence that it cannot (White, 1976; Evans and Simon, 1975). In his calculations, Finkelstein has used the diffusion constant o f water and nonelectrolytes in water as a model for the diffusion constant o f these molecules in the membrane interior . As the diffusion constant is inversely propor t iona l to the viscosity, f rom the Stokes-Einstein equat ion one would p resume the bilayer inter ior to be about lcP. T h e viscosities of water and n-hexadecane at 20°C are 1.002 and 3.34 cP, respectively (Handbook o f Chemistry and Physics, 55th edition), whereas the microviscosity o f lipid bilayers and plasma membranes , as de t e rmined by fluorescent probes (Azzi, 1975) and spin labels (Edidin, 1974), is the o rde r o f magni tude o f 1P. In part icular , Vanderkooi and Callis (1974) have found that at 20°C egg lecithin bilayers have a microviscosity o f 57.2 cP. Thus if the permeabil i ty t h rough a hexadecane "membrane" and a planar lipid bilayer are the same, and the viscosity o f the bilayer is two orders o f magni tude h igher than that o f n-hexadecane , then the diffusion constant o f water in a bilayer should be about two orders o f magni tude lower in a bilayer than n-hexadecane. Should this be the case, then ei ther the part i t ion coefficient for water in planar lipid bilayers is much h igher than for n-hexadecane , or the presence o f the hydrocarbon solvent, n-decane, in the m em b ran e reduced the viscosity o f the bilayer. We suggest that both these effects may be important . I f the membrane thickness is 50 ,~ and the diffusion constant is r educed by, at most, a factor o f 100, then the parti t ion coefficient o f water in the bilayer must be 100 times greater than that o f an organic liquid to maintain the same permeability. This factor may be accounted for in a n u m b e r of ways. First, the parti t ion coefficient between the bilayer inter ior and water for molecules with ei ther a net