Intercellular domain

Figure 7 The possible mechanisms involved in the effect of penetration enhancers on the lipid organization of the intercellular domains in the stratum corneum. (A) Intercalation of the enhancer in the lipid lamellae. (B) Phase separation between enhancer and skin lipids in the lamellae. (C) Phase separation between lipid lamellae and an enhancer-rich phase. (D) Intercalation of the enhancer in the lipid lamellae and simultaneous phase separation between lipid lamellae and enhancer. (E) Phase separation within the lamellae and separation between an enahncer-rich phase and the lamellar phase. (F) Disappearance of the lamellar phases.

Only a few laser scanning confocal microscopy (LSCM) studies have examined the passive permeation pathways of molecules across the skin. Cullander and Guy [36] showed that calcein, a multiply charged fluorophore, penetrates minimally into the SC of hairless mouse skin (HMS). Similar studies by Turner et al. [37a] have confirmed this observation. Indeed, it is the hydrophilic, charged nature of calcein that prevents its facile partitioning into the lipophilic intercellular spaces of the SC. Although some penetration of calcein into the SC intercellular domains, and into the pilary canal of the hair follicles, is observed, the total passive epidermal transport of calcein was negligible. 

While comeocytes can be considered to be hydrophilic domains, they are surrounded by a lipid-rich matrix mainly comprising ceramides, free fatty acids and cholesterol (Downing et al, 1987). Thus, the intercellular domain is predominantly a lipophilic environment. This combination imparts a degree of amphiphobicity upon... 

Transmembrane proteins have three regions or domains that can be defined the domain in the bilayer, the domain outside the cell (called the extracellular domain), and the domain inside the cell (called the intercellular domain). Even though a cell membrane is somewhat fluid, the orientation of transmembrane proteins does not change. The proteins are so large that the rate for them to change orientation is extremely small. Thus, the extracellular part of the transmembrane protein is always outside the cell and the intercellular portion is always inside. 

Hepatocytes are the commonest cell type found in the liver, constituting about 70% of the total liver mass. The plasma membranes of these cells have three functional domains the sinusoidal domain, an intercellular domain with gap junctions that is the contact area between hepatocytes, and the canalicular domain, where many of the hepatic secretory functions are performed. The hepatocytes are arranged in single cell layers around sinusoids, which are vascular capillary vessels connected to the hepatic portal vein and hepatic artery the perisinusoidal space of Disse separates the endothelial cell from the hepatocytes. Fenestrations (or windows) in the cells lining the sinusoids allow the formation of hepatic lymph fluid and the movement of proteins into the space of Disse. The lymph leaves the liver through the lymphatic vessels, the lymph nodes, and the thoracic duct, although a small proportion leaves the liver through lymph vessels associated with the hepatic vein. 

Elias and his co-workers have popularized a model which views the stratum corneum as a brick-and-mortar structure (Elias and Menon 1991). The bricks are protein-rich corneocytes separated by lipid-rich intercellular domains consisting of stacks of bilaminar membranes. Excellent reviews of the complex structure of the stratum corneum and the dynamics of its behavior have been presented by Menon and Fartasch Menon and Ghadially 1997 Farasch et al. 1993). 

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