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. 1999 Sep;77(3):1268–1283. doi: 10.1016/S0006-3495(99)76978-X

An analysis of the size selectivity of solute partitioning, diffusion, and permeation across lipid bilayers.

S Mitragotri 1, M E Johnson 1, D Blankschtein 1, R Langer 1
PMCID: PMC1300418  PMID: 10465741

Abstract

The lipid bilayers of cell membranes are primarily responsible for the low passive transport of nonelectrolytes across cell membranes, and for the pronounced size selectivity of such transport. The size selectivity of bilayer permeation has been hypothesized to originate from the hindered transport of solutes across the ordered-chain region. In this paper, we develop a theoretical description that provides analytical relationships between the permeation properties of the ordered-chain region of the lipid bilayer (partition and diffusion coefficients) and its structural properties, namely, lipid chain density, free area, and order parameter. Emphasis is placed on calculating the size selectivity of solute partitioning, diffusion, and overall permeability across the ordered-chain region of the lipid bilayer. The size selectivity of solute partitioning is evaluated using scaled-particle theory, which calculates the reversible work required to create a cavity to incorporate a spherical solute into the ordered-chain region of the lipid bilayer. Scaled-particle theory is also used to calculate the work required to create a diffusion path for solutes in the interfacial region of the lipid bilayer. The predicted size dependence of the bilayer permeability is comparable to that observed experimentally. The dependence of solute partition and diffusion coefficients on the bilayer structural parameters is also discussed.

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Selected References

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  1. Akeson M. A., Munns D. N. Lipid bilayer permeation by neutral aluminum citrate and by three alpha-hydroxy carboxylic acids. Biochim Biophys Acta. 1989 Sep 4;984(2):200–206. doi: 10.1016/0005-2736(89)90217-4. [DOI] [PubMed] [Google Scholar]
  2. Brunner J., Graham D. E., Hauser H., Semenza G. Ion and sugar permeabilities of lecithin bilayers: comparison of curved and planar bilayers. J Membr Biol. 1980 Dec 15;57(2):133–141. doi: 10.1007/BF01868999. [DOI] [PubMed] [Google Scholar]
  3. Chakrabarti A. C., Deamer D. W. Permeability of lipid bilayers to amino acids and phosphate. Biochim Biophys Acta. 1992 Nov 9;1111(2):171–177. doi: 10.1016/0005-2736(92)90308-9. [DOI] [PubMed] [Google Scholar]
  4. Diamond J. M., Katz Y. Interpretation of nonelectrolyte partition coefficients between dimyristoyl lecithin and water. J Membr Biol. 1974;17(2):121–154. doi: 10.1007/BF01870176. [DOI] [PubMed] [Google Scholar]
  5. Dix J. A., Kivelson D., Diamond J. M. Molecular motion of small nonelectrolyte molecules in lecithin bilayers. J Membr Biol. 1978 Jun 9;40(4):315–342. doi: 10.1007/BF01874162. [DOI] [PubMed] [Google Scholar]
  6. Han J., Herzfeld J. Macromolecular diffusion in crowded solutions. Biophys J. 1993 Sep;65(3):1155–1161. doi: 10.1016/S0006-3495(93)81145-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Huang P., Perez J. J., Loew G. H. Molecular dynamics simulations of phospholipid bilayers. J Biomol Struct Dyn. 1994 Apr;11(5):927–956. doi: 10.1080/07391102.1994.10508045. [DOI] [PubMed] [Google Scholar]
  8. Hummer G., Garde S., García A. E., Pohorille A., Pratt L. R. An information theory model of hydrophobic interactions. Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8951–8955. doi: 10.1073/pnas.93.17.8951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kumar V. V. Complementary molecular shapes and additivity of the packing parameter of lipids. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):444–448. doi: 10.1073/pnas.88.2.444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lieb W. R., Stein W. D. Biological membranes behave as non-porous polymeric sheets with respect to the diffusion of non-electrolytes. Nature. 1969 Oct 18;224(5216):240–243. doi: 10.1038/224240a0. [DOI] [PubMed] [Google Scholar]
  11. Nagle J. F. Area/lipid of bilayers from NMR. Biophys J. 1993 May;64(5):1476–1481. doi: 10.1016/S0006-3495(93)81514-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Poznansky M., Tong S., White P. C., Milgram J. M., Solomon A. K. Nonelectrolyte diffusion across lipid bilayer systems. J Gen Physiol. 1976 Jan;67(1):45–66. doi: 10.1085/jgp.67.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Seelig A., Seelig J. The dynamic structure of fatty acyl chains in a phospholipid bilayer measured by deuterium magnetic resonance. Biochemistry. 1974 Nov 5;13(23):4839–4845. doi: 10.1021/bi00720a024. [DOI] [PubMed] [Google Scholar]
  14. Vaz W. L., Almeida P. F. Microscopic versus macroscopic diffusion in one-component fluid phase lipid bilayer membranes. Biophys J. 1991 Dec;60(6):1553–1554. doi: 10.1016/S0006-3495(91)82190-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Vaz W. L., Clegg R. M., Hallmann D. Translational diffusion of lipids in liquid crystalline phase phosphatidylcholine multibilayers. A comparison of experiment with theory. Biochemistry. 1985 Jan 29;24(3):781–786. doi: 10.1021/bi00324a037. [DOI] [PubMed] [Google Scholar]
  16. Walter A., Gutknecht J. Permeability of small nonelectrolytes through lipid bilayer membranes. J Membr Biol. 1986;90(3):207–217. doi: 10.1007/BF01870127. [DOI] [PubMed] [Google Scholar]
  17. White S. H., King G. I. Molecular packing and area compressibility of lipid bilayers. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6532–6536. doi: 10.1073/pnas.82.19.6532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. White S. H. The lipid bilayer as a "solvent" for small hydrophobic molecules. Nature. 1976 Jul 29;262(5567):421–422. doi: 10.1038/262421a0. [DOI] [PubMed] [Google Scholar]
  19. Xiang T. X. A computer simulation of free-volume distributions and related structural properties in a model lipid bilayer. Biophys J. 1993 Sep;65(3):1108–1120. doi: 10.1016/S0006-3495(93)81156-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Xiang T. X., Anderson B. D. Influence of chain ordering on the selectivity of dipalmitoylphosphatidylcholine bilayer membranes for permeant size and shape. Biophys J. 1998 Dec;75(6):2658–2671. doi: 10.1016/S0006-3495(98)77711-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Xiang T. X., Anderson B. D. Molecular distributions in interphases: statistical mechanical theory combined with molecular dynamics simulation of a model lipid bilayer. Biophys J. 1994 Mar;66(3 Pt 1):561–572. doi: 10.1016/s0006-3495(94)80833-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Xiang T. X., Anderson B. D. Permeability of acetic acid across gel and liquid-crystalline lipid bilayers conforms to free-surface-area theory. Biophys J. 1997 Jan;72(1):223–237. doi: 10.1016/S0006-3495(97)78661-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Xiang T. X., Anderson B. D. Substituent contributions to the transport of substituted p-toluic acids across lipid bilayer membranes. J Pharm Sci. 1994 Oct;83(10):1511–1518. doi: 10.1002/jps.2600831027. [DOI] [PubMed] [Google Scholar]
  24. Xiang T. X., Anderson B. D. The relationship between permeant size and permeability in lipid bilayer membranes. J Membr Biol. 1994 Jun;140(2):111–122. doi: 10.1007/BF00232899. [DOI] [PubMed] [Google Scholar]
  25. de Gier J. Osmotic behaviour and permeability properties of liposomes. Chem Phys Lipids. 1993 Sep;64(1-3):187–196. doi: 10.1016/0009-3084(93)90065-b. [DOI] [PubMed] [Google Scholar]

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