Mechanical forces associated with blood flow play important roles in the acute control of vascular tone, the regulation of arterial structure and remodeling, and the localization of atherosclerotic lesions. Major regulation of the blood vessel responses occurs by the action of hemodynamic shear stresses on the endothelium. The transmission of hemodynamic forces throughout the endothelium and the mechanotransduction mechanisms that lead to biophysical, biochemical, and gene regulatory responses of endothelial cells to hemodynamic shear stresses are reviewed.

/pdf/flow-mediated-endothelial-mechanotransduction-281f54bq52.pdf

Flow-mediated endothelial mechanotransduction

Certain junctions between ependymal cells, between astrocytes, and between some electrically coupled neurons have heretofore been regarded as tight, pentalaminar occlusions of the intercellular cleft. These junctions are now redefined in terms of their configuration after treatment of brain tissue in uranyl acetate before dehydration. Instead of a median dense lamina, they are bisected by a median gap 20–30 A wide which is continuous with the rest of the interspace. The patency of these "gap junctions" is further demonstrated by the penetration of horseradish peroxidase or lanthanum into the median gap, the latter tracer delineating there a polygonal substructure. However, either tracer can circumvent gap junctions because they are plaque-shaped rather than complete, circumferential belts. Tight junctions, which retain a pentalaminar appearance after uranyl acetate block treatment, are restricted primarily to the endothelium of parenchymal capillaries and the epithelium of the choroid plexus. They form rows of extensive, overlapping occlusions of the interspace and are neither circumvented nor penetrated by peroxidase and lanthanum. These junctions are morphologically distinguishable from the "labile" pentalaminar appositions which appear or disappear according to the preparative method and which do not interfere with the intercellular movement of tracers. Therefore, the interspaces of the brain are generally patent, allowing intercellular movement of colloidal materials. Endothelial and epithelial tight junctions occlude the interspaces between blood and parenchyma or cerebral ventricles, thereby constituting a structural basis for the blood-brain and blood-cerebrospinal fluid barriers.

/pdf/junctions-between-intimately-apposed-cell-membranes-in-the-21o1r7s5bh.pdf

Junctions between intimately apposed cell membranes in the vertebrate brain

https://science.sciencemag.org/content/sci/177/4053/949.full.pdf

Lectins: cell-agglutinating and sugar-specific proteins.

During object manipulation tasks, the brain selects and implements action-phase controllers that use sensory predictions and afferent signals to tailor motor output to the physical properties of the objects involved. Analysis of signals in tactile afferent neurons and central processes in humans reveals how contact events are encoded and used to monitor and update task performance.

Coding and use of tactile signals from the fingertips in object manipulation tasks

Adjacent cells share ions, second messengers and small metabolites through intercellular channels which are present in gap junctions. This type of intercellular communication permits coordinated cellular activity, a critical feature for organ homeostasis during development and adult life of multicellular organisms. Intercellular channels are structurally more complex than other ion channels, because a complete cell-to-cell channel spans two plasma membranes and results from the association of two half channels, or connexons, contributed separately by each of the two participating cells. Each connexon, in turn, is a multimeric assembly of protein subunits. The structural proteins comprising these channels, collectively called connexins, are members of a highly related multigene family consisting of at least 13 members. Since the cloning of the first connexin in 1986, considerable progress has been made in our understanding of the complex molecular switches that control the formation and permeability of intercellular channels. Analysis of the mechanisms of channel assembly has revealed the selectivity of inter-connexin interactions and uncovered novel characteristics of the channel permeability and gating behavior. Structure/function studies have begun to provide a molecular understanding of the significance of connexin diversity and demonstrated the unique regulation of connexins by tyrosine kinases and oncogenes. Finally, mutations in two connexin genes have been linked to human diseases. The development of more specific approaches (dominant negative mutants, knockouts, transgenes) to study the functional role of connexins in organ homeostasis is providing a new perception about the significance of connexin diversity and the regulation of intercellular communication.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1996.0001q.x

Connections with connexins: the molecular basis of direct intercellular signaling

The general and familiar idea of the cell membrane is that of a barrier to diffusion encompassing the entire cell surface. This idea derives largely from work with a few cell types: nerve, striated muscle, blood, and gamete cells. These are, however, rather peculiar cells. They are generally not in direct contact with each other but are separated by wide fluid-filled spaces. I shall deal here with the question of what happens to the diffusion barrier when two cell membranes are brought close together. This states the question for the general case of cell association; most tissues, by far, are built of cells in close surface contact. I chose epithelial cells for a study of this question. These cells have several advantages. Their areas of membrane contact are large, and their size permits direct conductance measurements. The giant salivary gland cells of Drosophila and Chironornus were particularly suitable in this respect (FIGURE 1 ) .

Permeability of membrane junctions

Membrane permeability of an epithelial cell junction (Drosophila salivary gland) was examined with intracellular microelectrodes and with fluorescent tracers. In contrast to the non-junctional cell membrane surface, which has a low permeability to ions (10(-4) mho/cm(2)), the junctional membrane surface is highly permeable. In fact, it introduces no substantial restriction to ion flow beyond that in the cytoplasm; the resistance through a chain of cells (150 ohm cm) is only slightly greater than in extruded cytoplasm (100 ohm cm). The diffusion resistance along the intercellular space to the exterior, on the other hand, is very high. Here, there exists an ion barrier of, at least, 10(4) ohm cm(2). As a result, small ions and fluorescein move rather freely from one cell to the next, but do not leak appreciably through the intercellular space to the exterior. The organ here, rather than the single cell, appears to be the unit of ion environment. The possible underlying structural aspects are discussed.

https://rupress.org/jcb/article-pdf/22/3/565/1067437/565.pdf

STUDIES ON AN EPITHELIAL (GLAND) CELL JUNCTION I. Modifications of Surface Membrane Permeability

EVIDENCE for direct cell-to-cell communication is now available for a wide variety of epithelial tissues1–4. At the surfaces of cell contact (junctional surfaces), the cell membranes in these tissues are normally so permeable that many cellular ions and molecules may diffuse rather freely from one cell interior to the next. This report deals with the question of whether cellular communication of this kind is involved in the control of tissue growth.

Intercellular Communication and the Control of Tissue Growth: Lack of Communication between Cancer Cells

The surface structure of a gland epithelium (Drosophila salivary gland), particularly that at the junction between cells, was examined under the electron microscope. The junctional surface, which in the preceding paper was shown to be highly permeable to ions, has the following structural characteristics. About two-thirds of it are profusely infolded; the surface membranes of adjoining cells interdigitate and present desmosomes. The width of the intercellular space varies considerably. The remainder of the junctional surface, the third that abuts on the lumen, is rather straight. Here, the cell membranes are aligned parallel at a distance of 150 A, and interconnected at regular intervals of 100 A. The connecting material has a high electron opacity, and is about as thick as the cell membranes, but, unlike the latter, has no resolvable unit membrane structure. The surface at the cell base, which in the preceding paper was shown to be rather impermeable, is infolded and resembles the infolded junctional region. The luminal surface exhibits microvilli. Critical surface dimensions are given, and the implications of surface structure in intercellular permeability are discussed.

https://rupress.org/jcb/article-pdf/22/3/587/1067445/587.pdf

Studies on an epithelial (gland) cell junction. ii. surface structure.

1. An analysis is made of the transmission of mechanical forces through the Pacinian corpuscle. In particular, forces are analysed which produce pressure differences at the centre of the corpuscle and lead to excitation of the sensory nerve ending.2. The main structural elements in force transmission through the corpuscle are the lamellae, their interconnexions, and the interlamellar fluid. The two former provide the elastic elements and constraint for the fluid; and the latter, the viscous elements. The mechanical equivalent incorporating these elements is a system of dashpots (the lamellar surfaces and the interlamellar fluid) and springs (the lamellae and their interconnexions); it is a mechanical filter which suppresses low frequencies. The dynamic and static patterns of lamella displacements in the equivalent are in close agreement with those observed in Pacinian corpuscles.3. Steady-state and transient pressure fields were determined for the equivalent. Under static compression, only elastic forces exist in the corpuscle. Analysis shows that such forces are transmitted poorly from periphery to centre through the lamellated structure. The compliance of the lamellar interconnexions is so high in relation to that of the lamellae themselves, that most of the pressure load is carried by the outer lamellae. As a result, only a small fraction of the steady-state pressure at the outer surface reaches the centre of the corpuscle where the sensory ending is located. This is the mechanical basis of receptor adaptation.4. Under dynamic compression, viscous forces develop in the corpuscle; and these account for most of the pressure at times too early for development of elastic deformations. Analysis shows that such forces are transmitted well. For example, if a typical corpuscle of 500mu diameter is compressed by 20mu linearly during 2 msec, the pressure differences near to the centre of the corpuscle are initially as high as at the periphery, and stay within the same order throughout the process of compression. In general, pressure at the centre increases steeply with velocity of compression. This explains the marked velocity dependence of the generator response of the sensory ending.If, in the foregoing example, the 20mu compression is held fixed after 2 msec, the pressure differences at the centre fall abruptly to near zero with the onset of the static phase. The duration of pressure transients at the centre approximates that of the ;active' phase of the generator current of the sensory ending derived from experiments, as expected in a causal relationship: pressure difference --> generator current. Taken together with the earlier experimental finding of marked prolongation of generator response in corpuscles partially stripped of lamellae (Loewenstein & Mendelson, 1965), this result warrants the conclusion that the mechanical filter action of the corpuscle is the rate-limiting factor in generator response adaptation.5. When the corpuscle is released from compression, energy stored in the elastic elements during compression is released and consumed in viscous flow. Thus, viscous pressure is produced anew. The magnitude of this pressure depends on the velocity of release. The pressure distribution is rotated by 90 degrees with respect to that in compression; i.e. during release, compression occurs once again, but this time at right angles to the direction of initial compression. Experiments show that the sensory ending does not discriminate such a rotation; the polarity and order of magnitude of the generator response to compression in one plane are the same as in another. Analysis shows that considerable pressure differences may be developed at the centre of the corpuscle during releases at physiological velocities. For instance, in a passive return from a compression of 20mu, the pressure difference at the centre (and the generator current) is of the same order of magnitude as that in a compression of the velocity in 4. This accounts for the ;off'-response of the sensory ending in purely mechanical terms.

Werner R. Loewenstein

Papers

Permeability of membrane junctions

STUDIES ON AN EPITHELIAL (GLAND) CELL JUNCTION I. Modifications of Surface Membrane Permeability

Intercellular Communication and the Control of Tissue Growth: Lack of Communication between Cancer Cells

Studies on an epithelial (gland) cell junction. ii. surface structure.

Mechanical transmission in a Pacinian corpuscle. An analysis and a theory