Biochemistry - The Chemical Reactions of Living Cells, Volume 1 - D. Metzler 1980

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Multicellular Organisms
Intercellular Contacts and Interactions

When studying Multicellular Organisms, we face two fundamental questions: first, how do Cells connect with each other, and second, how do they interact in a specific manner?

To answer the first question, let us note that plant cells are surrounded by a thick Cell wall that binds them together and holds them in place. Animals lack rigid cell walls, yet their cells remain connected through highly specific mechanisms. Otherwise, we would all simply fall apart.

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FIG. 1-11. Cytology/cytology/93.html">ELECTRON MICROGRAPHS OF Three types of Intercellular junctions. A. Tight junction (zona occludens) between rat Small Intestine epithelial cells, obtained by freeze-fracture Replication. Tight junctions appear as a network of ridges and grooves, representing sites of membrane fusion. Microvilli are visible at the bottom of the figure. (Friend D. S., Gilula N. B., J. Cell Biology, 53, 771, 1972.)

FIG. 1-11. B. Ultrathin section through a tight junction between mouse hepatocytes. Arrows indicate sites of membrane fusion. (Gilula N. B., in Cellular Membranes and Tumor Cells, p. 221. Copyright 1975 by the Williams and Wilkins Co., Baltimore)

FIG. 1-11. C. Septate junction in mollusk ciliary epithelium; freeze-fracture preparation. Junctions of this type completely encircle the cells. The "naked" surface is covered by parallel rows of membrane particles corresponding to the distribution of intercellular septa visible in ultrathin sections. In membrane regions outside the contact area, particles are distributed irregularly [44].

FIG. 1-11. D. Ultrathin section of a septate junction of the same type as in Fig. C. The Plasma Membranes of two cells are joined by electron-dense plates, or septa, regularly arranged in the intercellular space. Note the Golgi apparatus at the bottom of the micrograph [44].

FIG. 1-11. E. Desmosomes (macula adherens) in rat intestinal epithelium. A wide intercellular space (25–35 nm) containing electron-dense material, two parallel cell membranes, and a dense plaque with converging tonofilaments permeating the Cytoplasm are visible [44].

a. Cell contacts and junctions

Many epithelial cells, such as those in renal tubules or glands, form tight junctions with one another. In such contacts, the outer Regions of the membranes fuse at intervals (Fig. 1-3) [44, 45]. Electron microscopic studies of freeze-fractured tissue surfaces (Supplement 1-B) reveal regions where cells are encircled by a band of tight junction, sometimes called a zonula occludens or terminal bar (Fig. 1-11). Tight junctions between endothelial cells of Brain capillaries prevent the free diffusion of substances from the Blood into brain cells, thereby forming the blood-brain barrier [46].

Invertebrate epithelial cells are encircled by another type of junction known as septate desmosomes, or adhesive belts. Here, the ~18 nm space between the membranes of adjacent cells is bridged at numerous points by thin cross-filaments. In the desmosome region, accumulations of electron-dense material adhere to the membranes of the contacting cells, serving as attachment sites for numerous fine filaments (microfilaments) approximately 6–10 nm in diameter [47].

In addition to tight junctions, extensive intercellular zones with a 10–20 nm gap between adjacent cells are frequently observed. In this region, microfilaments with a diameter of 6.0 nm adhere to the cytoplasmic side of the membrane.

Freeze-fracture preparations of such Gap Junctions reveal regular polygonal structures forming a lattice with a 10 nm periodicity. Gap junctions apparently represent areas of firm Cell Adhesion and serve as the primary pathway for Intercellular Communication.

FIG. 1-11. F. Fracture surface passing through gap junction regions between cultured cells. Both large and small (indicated by arrow) areas are visible [44].

b. Communicative cell junctions

Aside from direct physical contacts, cells must possess other mechanisms for exchanging information; otherwise, their coordinated growth and differentiation would be impossible. One mode of communication involves the exchange of chemical substances through specialized contact sites between cells [48]. Among the numerous Examples highlighting Structure/19.html">The Importance of communicative junctions is The phenomenon of cellular "electrical coupling." Typically, cell membranes exhibit very high electrical resistance; however, the membranes of contiguous cells contain low-resistance patches—evidently corresponding to gap junction areas [49]. One of the most sophisticated forms of communicative junction is the synapse, a specialized contact between Neurons. A Nerve Impulse propagating along the membrane of one neuron stimulates the release of a quantum of a chemical mediator, which diffuses across the synaptic cleft and triggers a nerve impulse In the second neuron.

FIG. 1-11. G. Gap junctions, ultrathin section [44].

It has been suggested that Cancer cells form fewer communicative junctions than healthy cells [50], but tissue culture experiments do not support this view [51].

c. Cell Recognition

Cells of higher organisms must be able to "recognize" other cells in order to determine whether they are identical, belong to other Tissues, or are "foreign".

Let us consider a particularly fascinating experiment with Sponges, whose cells were separated by Treatment with the enzyme Trypsin (which digests the intercellular protein "cement"). When the dissociated cells of orange and yellow sponges are mixed together, they reaggregate and gradually form new miniature sponges, with orange cells binding exclusively to orange cells, and yellow cells to yellow cells [52, 53]. Similar results were obtained using cultured embryonic Liver, Kidney, and brain cells. When these cultures were mixed, liver cells adhered only to liver cells, and kidney cells only to kidney cells. How do cells "recognize" one another? Current biochemical research aims to provide the answer to this question.

During wound healing, epithelial cells proliferate and migrate across the wound surface until they come into contact with one another. A similar phenomenon, known as contact inhibition, is exhibited by cells and tissue cultures growing on a Glass surface, resulting in The formation of a single-cell-thick layer (a monolayer). Cultured tumor cells, by contrast, do not cease growth upon contact and pile up on top of one another, apparently due to a deficiency in the mechanisms of Cell recognition and intercellular communication. Uncovering the biochemical mechanism behind this phenomenon would be of tremendous importance for medicine.