The Journal of Membrane Biology

, Volume 140, Issue 2, pp 111–122

The relationship between permeant size and permeability in lipid bilayer membranes


  • T. -X. Xiang
    • Department of Pharmaceutics and Pharmaceutical ChemistryUniversity of Utah
  • B. D. Anderson
    • Department of Pharmaceutics and Pharmaceutical ChemistryUniversity of Utah

DOI: 10.1007/BF00232899

Cite this article as:
Xiang, T.-. & Anderson, B.D. J. Membarin Biol. (1994) 140: 111. doi:10.1007/BF00232899


Permeability coefficients (Pm) across planar egg lecithin/decane bilayers and bulk hydrocarbon/water partition coefficients (Kw→hc) have been measured for 24 solutes with molecular volumes, V, varying by a factor of 22 and Pm values varying by a factor of 107 to explore the chemical nature of the bilayer barrier and the effects of permeant size on permeability. A proper bulk solvent which correctly mimics the microenvironment of the barrier domain was sought. Changes in Pm/Kw→hc were then ascribed to size-dependent partitioning and/or size-dependent diffusivity. The diffusion coefficient-size dependency was described by Dbarrier = D0/Vn. When n-decane was used as a reference solvent, the correlation between log Pm/Kw→hc and log V was poor (r = 0.56) with most of the lipophilic (hydrophilic) permeants lying below (above) the regression line. Correlations improved significantly (r = 0.87 and 0.90, respectively) with more polarizable solvents, 1-hexadecene and 1,9-decadiene. Values of the size selectivity parameter n were sensitive to the reference solvent (n = 0.8 ± 0.3, 1.2 ± 0.1 and 1.4 ± 0.2, respectively, for decane, hexadecene, and decadiene). Decadiene was selected as the most suitable reference solvent. The value for n in bilayer transport is higher than that for bulk diffusion in decane (n = 0.74±0.10), confirming the steep dependence of bilayer permeability on molecular size. Statistical mechanical theory recently developed by the authors suggests that a component of this steep size dependence may reside in size-dependent solute partitioning into the ordered chain region of bilayers. This theory, combined with the above diffusion model, yielded the relationship, Pm/KW→hc=D0exp(™αV)Vn. A fit of the experimental data to this model gave the best fit (r=0.93) with α = 0.0053±0.0021 and n=0.8 ± 0.3, suggesting that both diffusion and partitioning mechanisms may play a role in determining the size dependence of lipid bilayer permeabilities.

Key words

PermeabilityTransportBilayersSize dependencePartition coefficientsDiffusion coefficients

Copyright information

© Springer-Verlag New York Inc 1994