Intercellular cleft

An intercellular cleft is a channel between two cells through which molecules may travel and gap junctions and tight junctions may be present. Most notably, intercellular clefts are found between epithelial cells and the endothelium of blood vessels and lymphatic vessels, also helping to form the blood-nerve barrier surrounding nerves. Intercellular clefts are important for allowing the transportation of fluids and small solute matter through the endothelium.

The dimensions of intercellular clefts vary throughout the body, however cleft lengths have been determined for a series of capillaries. The average cleft length for capillaries is about 20m/cm². The depths of the intercellular clefts, measured from the luminal to the abluminal openings, vary among different types of capillaries, but the average is about 0.7 μm. The width of the intercellular clefts is about 20 nm outside the junctional region (i.e. in the larger part of the clefts). In intercellular clefts of capillaries, it has been calculated that the fractional area of the capillary wall occupied by the intercellular cleft is 20m/cm² x 20 nm (length x width)= 0.004 (0.4%). This is the fractional area of the capillary wall exposed for free diffusion of small hydrophilic solutes and fluids⁵.

The intercellular cleft is imperative for cell-cell communication. The cleft contains gap junctions, tight junctions, desmosomes, and adheren proteins, all of which help to propagate and/or regulate cell communication through signal transduction, surface receptors, or a chemogradient. In order for a molecule to be taken into the cell either by endocytosis, phagocytosis, or receptor-mediated endocytosis, often that molecule must first enter through the cleft. The intercellular cleft itself is a channel, but what flows through the channel, like ions, fluid, and small molecules and what proteins or junctions give order to the channel is critical for the life of the cells that border the intercellular cleft.

Research at the cell level can deliver proteins, ions, or specific small molecules into the intercellular cleft as a means of injecting a cell. This method is especially useful in cell-to-cell propagation of infectious cytosolic protein aggregates. In one study, protein aggregates from yeast prions were released into a mammalian intercellular cleft and were taken up by the adjacent cell, as opposed to direct cell transfer. This process would be similar to the secretion and transmission of infectious particles through the synaptic cleft between cells of the immune system, as seen in retroviruses. Understanding the routes of intercellular protein aggregate transfer, particularly routes involving clefts is imperative in understanding the progressive spreading of this infection⁸.

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