The intriguing molecular dynamics of Cer[EOS] in rigid skin barrier lipid layers requires improvement of the model |
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Institution: | 1. Institute of Medical Physics and Biophysics, University of Leipzig, Leipzig, Germany;2. Skin Barrier Research Group, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic;3. Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia;4. Institut Laue-Langevin, Grenoble, France;5. Department of Analytical Chemistry, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic;6. Institute of Macromolecular Chemistry, Czech Academy of Science in Prague, Prague, Czech Republic |
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Abstract: | Omega-O-acyl ceramides such as 32-linoleoyloxydotriacontanoyl sphingosine (CerEOS]) are essential components of the lipid skin barrier, which protects our body from excessive water loss and the penetration of unwanted substances. These ceramides drive the lipid assembly to epidermal-specific long periodicity phase (LPP), structurally much different than conventional lipid bilayers. Here, we synthesized CerEOS] with selectively deuterated segments of the ultralong N-acyl chain or deuterated or 13C-labeled linoleic acid and studied their molecular behavior in a skin lipid model. Solid-state 2H NMR data revealed surprising molecular dynamics for the ultralong N-acyl chain of CerEOS] with increased isotropic motion toward the isotropic ester-bound linoleate. The sphingosine moiety of CerEOS] is also highly mobile at skin temperature, in stark contrast to the other LPP components, N-lignoceroyl sphingosine acyl, lignoceric acid, and cholesterol, which are predominantly rigid. The dynamics of the linoleic chain is quantitatively described by distributions of correlation times and using dynamic detector analysis. These NMR results along with neutron diffraction data suggest an LPP structure with alternating fluid (sphingosine chain-rich), rigid (acyl chain-rich), isotropic (linoleate-rich), rigid (acyl-chain rich), and fluid layers (sphingosine chain-rich). Such an arrangement of the skin barrier lipids with rigid layers separated with two different dynamic “fillings” i) agrees well with ultrastructural data, ii) satisfies the need for simultaneous rigidity (to ensure low permeability) and fluidity (to ensure elasticity, accommodate enzymes, or antimicrobial peptides), and iii) offers a straightforward way to remodel the lamellar body lipids into the final lipid barrier. |
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Keywords: | stratum corneum models NMR spectroscopy neutron diffraction lipid assembly long periodicity phase molecular dynamics lipid chain order CP"} {"#name":"keyword" "$":{"id":"kwrd0050"} "$$":[{"#name":"text" "_":"cross-polarization ILL"} {"#name":"keyword" "$":{"id":"kwrd0060"} "$$":[{"#name":"text" "_":"Institut Laue-Langevin LA"} {"#name":"keyword" "$":{"id":"kwrd0070"} "$$":[{"#name":"text" "_":"lignoceric acid LPP"} {"#name":"keyword" "$":{"id":"kwrd0080"} "$$":[{"#name":"text" "_":"long periodicity phase MAS"} {"#name":"keyword" "$":{"id":"kwrd0090"} "$$":[{"#name":"text" "_":"magic-angle spinning ND"} {"#name":"keyword" "$":{"id":"kwrd0100"} "$$":[{"#name":"text" "_":"neutron diffraction NSLD"} {"#name":"keyword" "$":{"id":"kwrd0110"} "$$":[{"#name":"text" "_":"neutron scattering length density NWAXS"} {"#name":"keyword" "$":{"id":"kwrd0120"} "$$":[{"#name":"text" "_":"near wide-angle X-ray scattering ppm"} {"#name":"keyword" "$":{"id":"kwrd0130"} "$$":[{"#name":"text" "_":"parts per million MD"} {"#name":"keyword" "$":{"id":"kwrd0140"} "$$":[{"#name":"text" "_":"molecular dynamics SAXS"} {"#name":"keyword" "$":{"id":"kwrd0150"} "$$":[{"#name":"text" "_":"small-angle X-ray scattering SC"} {"#name":"keyword" "$":{"id":"kwrd0160"} "$$":[{"#name":"text" "_":"stratum corneum SPP"} {"#name":"keyword" "$":{"id":"kwrd0170"} "$$":[{"#name":"text" "_":"short periodicity phase |
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