Lipid organization

A final example of the simulation of a complex system is a series of MD simulations of bilayer membranes. Membranes are crucial constituents of living organisms they are the scene for many important biological processes. Experimental data are known for model systems for example for the system sodium decanoate, decanol and water that forms smectic liquid crystalline structures at room temperature, with the lipids organized in bilayers. 

Wisniewska, A., J. Draus, and W. K. Subczynski. 2006. Is fluid mosaic model of biological membranes fully relevant Studies on lipid organization in model and biological membranes. Cell. Mol. Biol. Lett. 8 147-154. 

A. P. M. Lavrijsen, J. A. Bouwstra, G. S. Gooris, A. Weerheim, H. E. Bodde, and M. Ponec. Reduced skin barrier function parallels abnormal stratum comeum lipid organization in patients with lamellar ichthyosis. J. Invest. Dermatol. 105 619-624 (1995). 

M. W. de Jager, G. S. Gooris, I. P. Dolbnya, W. Bras, M. Ponec, and J. A. Bouwstra. Novel lipid mixtures based on synthetic ceramides reproduce the unique stratum corneum lipid organization. J. Lipid Res. 45 923-932 (2004). 

M. De Jager, G. Gooris, M. Ponec, and J. Bouwstra. Acylceramide head group architecture affects lipid organization in synthetic ceramide mixtures. J. Invest. Dermatol. 123 911-916 (2004). 

The Lipid Organization in Stratum Corneum and Model Systems Based on Ceramides... 

In Vitro Lipid Organization of Lipid Mixtures Prepared... 

FIGURE 11.3 Lipid organization in the 13 nm lamellar phase according to the sandwich model. 

The above results demonstrate that the unique stratum corneum lipid organization can be reproduced in vitro with mixtures based on cholesterol, free fatty acids, and a limited number of synthetic ceramides. The results further reveal that the formation of the LPP is rather insensitive toward changes in the total composition of cholesterol, CER, and free fatty acids over a wide range of molar ratios. This is in excellent agreement with the in vivo situation, in which a high interindividual variability in stratum corneum lipid composition usually does not lead to substantial changes in the lipid organization. 

The lipid organization in equimolar mixtures of cholesterol, synthetic CER, and free fatty acids closely resembles that in stratum corneum, as both LPP (12.2 nm) and SPP (5.4 nm) are present, the lateral packing of the lipids is orthorhombic, a minor fraction of cholesterol phase separates into crystalline domains, and no additional phases can be detected. Interestingly, free fatty acids are required for proper lipid organization, as only in their presence a dominant formation of the LPP could be detected. This might be related to the limited acyl chain length distribution present in these CER mixtures. 

The lipid organization in stratum corneum is very unusual. Two lamellar phases are present with periodicities of approximately 6 and 13 nm. This lipid organization can be reproduced in vitro with mixtures prepared from either isolated ceramides (from pig and human stratum corneum) or synthetic ceramides. However, for the formation of the long periodicity phase the presence of acyl ceramides in the lipid mixtures is very crucial. The phase behavior of the lipid mixtures provides important information to explain the deviation in phase behavior in diseased skin. 

Pilgram, G.S.K., et al. 1999. Electron diffraction provides new information on human stratum corneum lipid organization studied in relation to depth and temperature. J Invest Dermatol 113 403. 

Bouwstra, J.A., et al. 1999. Cholesterol sulfate and calcium affect stratum corneum lipid organization over a wide temperature range. J Lipid Res 40 2303. 

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