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Biologische Systeme und Medizin Poster: Mi., 14:00–16:30 M-P212
New insights into the molecular backgrounds of recessive X-linked ichthyosis;
an X-ray and neutron scattering study
Jarmila Zbytovská 1 , Mikhail A. Kiselev 2 , Sergio S. Funari 3 , Vasil M.
Garamus 4 , Thomas Hauß 5 , Siegfried Wartewig 6 , Reinhard Neubert 6
1 Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 50005 Hradec
Králové, Czech Republic – 2 Frank Laboratory of Neutron Physics, JINR, Dubna,
Russia – 3 MPI of Colloids and Interfaces, Golm, *c/o HASYLAB, Hamburg, Germany
– 4 GKSS Research Centre, Geesthacht, Germany – 5 HMI, Berlin, Germany –
6 Institute of Pharmaceutical Technology and Biopharmacy, Martin-Luther-University
Halle-Wittenberg, Germany
Stratum corneum (SC), the outermost skin layer consisting of corneocytes which are
embedded in a lipid matrix, is responsible for the unique properties of the mammalian
skin. An aberrant composition of the SC lipids affects the regular skin functions. In
recessive X-linked ichthyosis (RXLI), decreased levels of cholesterol (CHOL) related
to the increased levels of cholesterol sulphate (CS) have been described. Currently,
the CS accumulation is considered to be the primary mechanism contributing to the
pathologic skin features. However, it is not enough elucidated yet, if the decreased
CHOL levels can also contribute to the abnormality of the RXLI skin.
This study aims to elucidate the role of CHOL in the SC on the molecular level. A
lipid model system mimicking the SC lipid composition has been developed. Small angle
X-ray diffraction on multilamellar vesicles has been used to determine the lamellar
repeat distance of the SC lipid membranes. This value decreases with the increasing
CHOL content in the membrane. Small angle neutron scattering on unilamellar
vesicles allowed calculating the membrane thickness parameter (dg) and the average
area per molecule of the membrane surface (A). An increase in the CHOL content in
the membrane induces a decrease in dg and an increase in A. Neutron diffraction on
multilamellar lipid films enabled us to obtain neutron scattering length density profiles
of the model systems. The membrane thickness, thickness of the membrane hydration
layer, thickness of the polar head groups as well as of the hydrocarbon chain regions
have been determined [1].
In conclusion, the reduced CHOL levels are wrongfully neglected in the RXLI pathophysiology.
Decreased CHOL concentration in the SC lipid membranes induces a decrease
in the required fluidity of the hydrocarbon chains and changes in the internal
membrane structure. Consequently, the SC lipid membranes become more rigid and
fragile and the skin function is strongly affected.
Financial support from the grants of the Federal State of Saxony-Anhalt (Project
3482A/1102L) and of the Ministry of Education of the Czech Republic
(MSM 0021620822) as well as from HMI, GKSS and DESY is gratefully acknowledged.
[1] Kiselev et al., Eur. Biophys. J. 34 (2005) 1030.