One of the major prerequisites for the existence of biological organisms is compartmentalization. This process is an important early step in biological evolution, when the first organisms dissociated themselves from the surrounding medium by the generation of a selectively permeable membrane. In more and more complex organisms, not only are cells separated from their environment but also organs, such as the brain, are protected from changes in the interstitial fluid. Ultimately, the whole organism generates a milieu interieur whose composition is monitored with great precision and kept within narrow limits that optimize body function. Compartmentalization in complex organisms, such as mammals, is achieved by specifically organized cells, such as endothelial cells (ECs) and epithelial cells. On the one hand, both cell types act as barriers that separate compartments. On the other hand, they both mediate the vectorial transport of solutes and macromolecules. The predominance of the “wall function” versus the “gate function” varies from the blood–brain barrier endothelium to the sinusoidal endothelium and from “tight” epithelia to “leaky” epithelia. The underlying cellular and molecular mechanisms appear, however, to be quite similar. The current chapter reviews these biophysical and biochemical similarities and attempts to delineate common principles of structure and function in endothelial and epithelial cells.

Special emphasis is thereby placed on the relation between asymmetry and net movement of small solutes. Asymmetry (i.e., polarity) of cell membrane transport properties is found in both epithelial and EC layers, and provides the basis for transcellular transport. Furthermore, the asymmetry of membrane transporters is discussed with regard to their different properties at the extra- and intracellular face.