Intercellular cleft

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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 often 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.

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Dimensions of intercellular cleft

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.

Communication via cleft

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 utilizing cleft communication

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.

Transport in intercellular cleft

Endothelial tight junctions are most commonly found in the intercellular cleft and provide for regulation of diffusion through the membranes. These links are most commonly found in the most apical aspect of the intercellular cleft. They prevent macromolecules from navigating the intercellular cleft and limit the lateral diffusion of intrinsic membrane proteins and lipids between the apical and basolateral cell surface domains. In the intercellular clefts of capillaries, tight junctions are the first structural barriers a neutrophil encounters as it penetrates the interendothelial cleft, or the gap linking the blood vessel lumen with the subendothelial space2. In capillary endothelium, plasma communicates with the interstitial fluid through the intercellular cleft. Blood plasma without the plasma proteins, red blood cells, and platelets pass through the intercellular cleft and into the capillary7.

Capillary intercellular clefts

Most notably, intercellular clefts are described in capillary blood vessels. The three types of capillary blood vessels are continuous, fenestrated, and discontinuous, with continuous being the least porous of the three and discontinuous capillaries being extremely high in permeability. Continuous blood capillaries have the smallest intercellular clefts, with discontinuous blood capillaries having the largest intercellular clefts, commonly accompanied with gaps in the basement membrane6.Often, fluid is forced out of the capillaries through the intercellular clefts. Fluid is push out through the intercellular cleft at the arterial end of the capillary because that's where the pressure is the highest. However, most of this fluid returns into the capillary at the venous end, creating capillary fluid dynamics. Two opposing forces achieve this balance; hydrostatic pressure and colloid osmotic pressure, using the intercellular clefts are fluid entrances and fluid exits4. In addition, the size of the intercellular clefts and pores in the capillary will influence this fluid exchange. The larger the intercellular cleft, the lesser the pressure and the more fluid will flow out the cleft. This enlargement of the cleft is caused by contraction of capillary endothelial cells, often by substances such as histamine and bradykinin. However, smaller intercellular clefts do not help this fluid exchange3. Along with fluid, electrolytes are also carried through this transport in the capillary blood vessels4. This mechanism of fluid, electrolyte, and also small solute exchange is especially important in renal glomerular capillaries3.

Intercellular cleft and BHB

Intercellular clefts also play a role in the formation of the blood-heart barrier (BHB). The intercellular cleft between endocardial endotheliocytes is 3 to 5 times deeper than the clefts between myocardial capillary endotheliocytes. Also, these clefts are often more twisting and have one or two tight junctions and zona adherens interacting with a circumferential actin filament band and several connecting proteins7. These tight junctions localize to the luminal side of the intercellular clefts, where the glycocalyx, which is important in cell–cell recognition and cell signaling, is more developed. The organization of the endocardial endothelium and the intercellular cleft help to establish the blood-heart barrier by ensuring an active transendothelial physicochemical gradient of various ions1.

Related Research Articles

<span class="mw-page-title-main">Capillary</span> Smallest type of blood vessel

A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: they convey blood between the arterioles and venules. These microvessels are the site of exchange of many substances with the interstitial fluid surrounding them. Substances which cross capillaries include water, oxygen, carbon dioxide, urea, glucose, uric acid, lactic acid and creatinine. Lymph capillaries connect with larger lymph vessels to drain lymphatic fluid collected in the microcirculation.

<span class="mw-page-title-main">Blood–brain barrier</span> Semipermeable capillary border that allows selective passage of blood constituents into the brain

The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from non-selectively crossing into the extracellular fluid of the central nervous system where neurons reside. The blood–brain barrier is formed by endothelial cells of the capillary wall, astrocyte end-feet ensheathing the capillary, and pericytes embedded in the capillary basement membrane. This system allows the passage of some small molecules by passive diffusion, as well as the selective and active transport of various nutrients, ions, organic anions, and macromolecules such as glucose and amino acids that are crucial to neural function.

<span class="mw-page-title-main">Epithelium</span> Tissue lining the surfaces of organs in animals

Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellular matrix. Epithelial tissues line the outer surfaces of organs and blood vessels throughout the body, as well as the inner surfaces of cavities in many internal organs. An example is the epidermis, the outermost layer of the skin.

<span class="mw-page-title-main">Lymph</span> Fluid that circulates throughout the lymphatic system

Lymph is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues to be recirculated. At the origin of the fluid-return process, interstitial fluid—the fluid between the cells in all body tissues—enters the lymph capillaries. This lymphatic fluid is then transported via progressively larger lymphatic vessels through lymph nodes, where substances are removed by tissue lymphocytes and circulating lymphocytes are added to the fluid, before emptying ultimately into the right or the left subclavian vein, where it mixes with central venous blood.

<span class="mw-page-title-main">Microcirculation</span> Circulation of the blood in the smallest blood vessels

The microcirculation is the circulation of the blood in the smallest blood vessels, the microvessels of the microvasculature present within organ tissues. The microvessels include terminal arterioles, metarterioles, capillaries, and venules. Arterioles carry oxygenated blood to the capillaries, and blood flows out of the capillaries through venules into veins.

<span class="mw-page-title-main">Extracellular fluid</span> Body fluid outside the cells of a multicellular organism

In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 60% of total body weight; women and the obese typically have a lower percentage than lean men. Extracellular fluid makes up about one-third of body fluid, the remaining two-thirds is intracellular fluid within cells. The main component of the extracellular fluid is the interstitial fluid that surrounds cells.

<span class="mw-page-title-main">Cell adhesion</span> Process of cell attachment

Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indirect interaction, where cells attach to surrounding extracellular matrix, a gel-like structure containing molecules released by cells into spaces between them. Cells adhesion occurs from the interactions between cell-adhesion molecules (CAMs), transmembrane proteins located on the cell surface. Cell adhesion links cells in different ways and can be involved in signal transduction for cells to detect and respond to changes in the surroundings. Other cellular processes regulated by cell adhesion include cell migration and tissue development in multicellular organisms. Alterations in cell adhesion can disrupt important cellular processes and lead to a variety of diseases, including cancer and arthritis. Cell adhesion is also essential for infectious organisms, such as bacteria or viruses, to cause diseases.

<span class="mw-page-title-main">Glomerulus (kidney)</span> Functional unit of nephron

The glomerulus is a network of small blood vessels (capillaries) known as a tuft, located at the beginning of a nephron in the kidney. Each of the two kidneys contains about one million nephrons. The tuft is structurally supported by the mesangium, composed of intraglomerular mesangial cells. The blood is filtered across the capillary walls of this tuft through the glomerular filtration barrier, which yields its filtrate of water and soluble substances to a cup-like sac known as Bowman's capsule. The filtrate then enters the renal tubule of the nephron.

The Starling equation describes the net flow of fluid across a semipermeable membrane. It is named after Ernest Starling. It describes the balance between capillary pressure, interstitial pressure, and osmotic pressure. The classic Starling equation has in recent years been revised. The Starling principle of fluid exchange is key to understanding how plasma fluid (solvent) within the bloodstream moves to the space outside the bloodstream.

Cell junctions are a class of cellular structures consisting of multiprotein complexes that provide contact or adhesion between neighboring cells or between a cell and the extracellular matrix in animals. They also maintain the paracellular barrier of epithelia and control paracellular transport. Cell junctions are especially abundant in epithelial tissues. Combined with cell adhesion molecules and extracellular matrix, cell junctions help hold animal cells together.

<span class="mw-page-title-main">Tight junction</span> Structure preventing inter-cell leakage

Tight junctions, also known as occluding junctions or zonulae occludentes, are multiprotein junctional complexes whose canonical function is to prevent leakage of solutes and water and seals between the epithelial cells. Tight junctions may also serve as leaky pathways by forming selective channels for small cations, anions, or water. Tight junctions are present mostly in vertebrates. The corresponding junctions that occur in invertebrates are septate junctions.

<span class="mw-page-title-main">Blood–testis barrier</span> A physical barrier between the blood vessels and the seminiferous tubules of the animal testes

The blood–testis barrier is a physical barrier between the blood vessels and the seminiferous tubules of the animal testes. The name "blood-testis barrier" is misleading in that it is not a blood-organ barrier in a strict sense, but is formed between Sertoli cells of the seminiferous tubule and as such isolates the further developed stages of germ cells from the blood. A more correct term is the "Sertoli cell barrier" (SCB).

Transcytosis is a type of transcellular transport in which various macromolecules are transported across the interior of a cell. Macromolecules are captured in vesicles on one side of the cell, drawn across the cell, and ejected on the other side. Examples of macromolecules transported include IgA, transferrin, and insulin. While transcytosis is most commonly observed in epithelial cells, the process is also present elsewhere. Blood capillaries are a well-known site for transcytosis, though it occurs in other cells, including neurons, osteoclasts and M cells of the intestine.

<span class="mw-page-title-main">VE-cadherin</span> Protein-coding gene in the species Homo sapiens

Cadherin 5, type 2 or VE-cadherin also known as CD144, is a type of cadherin. It is encoded by the human gene CDH5.

<span class="mw-page-title-main">Intestinal epithelium</span> Single-cell layer lining the intestines

The intestinal epithelium is the single cell layer that form the luminal surface (lining) of both the small and large intestine (colon) of the gastrointestinal tract. Composed of simple columnar epithelial cells, it serves two main functions: absorbing useful substances into the body and restricting the entry of harmful substances. As part of its protective role, the intestinal epithelium forms an important component of the intestinal mucosal barrier. Certain diseases and conditions are caused by functional defects in the intestinal epithelium. On the other hand, various diseases and conditions can lead to its dysfunction which, in turn, can lead to further complications.

Cell–cell interaction refers to the direct interactions between cell surfaces that play a crucial role in the development and function of multicellular organisms. These interactions allow cells to communicate with each other in response to changes in their microenvironment. This ability to send and receive signals is essential for the survival of the cell. Interactions between cells can be stable such as those made through cell junctions. These junctions are involved in the communication and organization of cells within a particular tissue. Others are transient or temporary such as those between cells of the immune system or the interactions involved in tissue inflammation. These types of intercellular interactions are distinguished from other types such as those between cells and the extracellular matrix. The loss of communication between cells can result in uncontrollable cell growth and cancer.

Transcellular transport involves the transportation of solutes by a cell through a cell. Transcellular transport can occur in three different ways active transport, passive transport, and transcytosis.

Microvasculature comprises the microvessels – venules and capillaries of the microcirculation, with a maximum average diameter of 0.3 millimeters. As the vessels decrease in size, they increase their surface-area-to-volume ratio. This allows surface properties to play a significant role in the function of the vessel.

Tight junction proteins are molecules situated at the tight junctions of epithelial, endothelial and myelinated cells. This multiprotein junctional complex has a regulatory function in passage of ions, water and solutes through the paracellular pathway. It can also coordinate the motion of lipids and proteins between the apical and basolateral surfaces of the plasma membrane. Thereby tight junction conducts signaling molecules, that influence the differentiation, proliferation and polarity of cells. So tight junction plays a key role in maintenance of osmotic balance and trans-cellular transport of tissue specific molecules. Nowadays is known more than 40 different proteins, that are involved in these selective TJ channels.

The blood-spinal cord barrier (BSCB) is a semipermeable anatomical interface that consists of the specialized small blood vessels that surround the spinal cord. While similar to the blood-brain barrier in function and morphology, it is physiologically independent and has several distinct characteristics. The BSCB is involved in many disorders affecting the central nervous system, including neurodegenerative diseases, pain disorders, and traumatic spinal cord injury. In conjunction with the blood-brain barrier, the BSCB contributes to the difficulty in delivering drugs to the central nervous system, which makes drug targeting of the BSCB an important goal in pharmaceutical research.

References

    1. Thiriet, M. (2015). Interactions between cardiac cell populations. In Diseases of the cardiac pump (1st ed., Vol. 7, pp. 59–61). Paris: Springer.
    2. Gabrilovich, D. (2013). Mechanisms of neutrophil migration. In The neutrophils new outlook for old cells (3rd ed., pp. 138–144). London: Imperial College Press;.
    3. Klabunde, R. (2014, April 30). Mechanisms of capillary exchange. Retrieved 2015, from http://www.cvphysiology.com/Microcirculation/M016.htm
    4. Marieb, E.N. (2003). Essentials of Human Anatomy and Physiology (Seventh ed.). San Francisco: Benjamin Cummings. ISBN   0-8053-5385-2.
    5. Chien, S. (1988). Mathematical models of intercellular clefts. In Vascular endothelium in health and disease (Vol. 242, pp. 3–5). New York City, New York: Plenum Press.
    6. Capillaries. (n.d.). Retrieved from http://www.udel.edu/biology/Wags/histopage/vascularmodelingpage/circsystempage/capillaries/capillaries.html
    7. Silberberg, A.(1988). Structure of the interendothelial cell cleft. Biorheology, 25(1–2),303–18.
    8. Hofmann, J., Denner, P., Naussbaum- Krammer, C., Kuhn, P., Suhre, M., Scheibel, T., ... Vorberg, I. (2013). Cell-to-cell propagation of infectious cytosolic protein aggregates. Proceedings of the National Academy of Sciences of the United States of America,110(15), 5951–5956–5951–5956. doi:10.1073/pnas.1217321110
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