Localization of Cholesterol and Fatty Acid in a Model Lipid Membrane: A Neutron Diffraction Approach

E. H. Mojumdar, D. Groen, G. S. Gooris, D. J. Barlow, M. J. Lawrence, B. Deme, J. A. Bouwstra*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)

Abstract

The intercellular lipid matrix of the skin's stratum corneum serves to protect the body against desiccation and simultaneously limits the passage of drugs and other xenobiotics into the body. The matrix is made up of ceramides, free fatty acids, and cholesterol, which are organized as two coexisting crystalline lamellar phases. In studies reported here, we sought to use the technique of neutron diffraction, together with the device of isotopic (HID) substitution, to determine the molecular architecture of the lamellar phase having a repeat distance of 53.9 +/- 0.3 angstrom. Using hydrogenous samples as well as samples incorporating perdeuterated (C24:0) fatty acids and selectively deuterated cholesterol, the diffraction data obtained were used to construct neutron scattering length density profiles. By this means, the locations within the unit cell were determined for the cholesterol and fatty acids. The cholesterol headgroup was found to lie slightly inward from the unit cell boundary and the tail of the molecule located 6.2 +/- 0.2 angstrom from the unit cell center. The fatty acid headgroups were located at the unit cell boundary with their acyl chains straddling the unit cell center. Based on these results, a molecular model is proposed for the arrangement of the lipids within the unit cell.

Original languageEnglish
Pages (from-to)911-918
Number of pages8
JournalBiophysical Journal
Volume105
Issue number4
DOIs
Publication statusPublished - 20 Aug 2013

Keywords

  • HUMAN STRATUM-CORNEUM
  • X-RAY-DIFFRACTION
  • PHASE-BEHAVIOR
  • PERCUTANEOUS PENETRATION
  • MOLECULAR-DYNAMICS
  • CERAMIDES
  • ORGANIZATION
  • MIXTURES
  • BILAYERS
  • SKIN

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