The glycocalyx (: glycocalyces or glycocalyxes), also known as the pericellular matrix and cell coat, is a layer of glycoproteins and glycolipids which surround the cell membranes of

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

, epithelial cells, and other cells. Animal epithelial cells have a fuzz-like coating on the external surface of their plasma membranes. This viscous coating is the glycocalyx that consists of several carbohydrate moieties of membrane glycolipids and glycoproteins, which serve as backbone molecules for support. Generally, the

carbohydrate A carbohydrate () is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms. The typical hydrogen-to-oxygen atomic ratio is 2:1, analogous to that of water, and is represented by the empirical formula (where ''m'' and ''n'' ...

portion of the glycolipids found on the surface of plasma membranes helps these molecules contribute to cell–cell recognition, communication, and intercellular adhesion. The glycocalyx is a type of identifier that the body uses to distinguish between its own healthy cells and transplanted tissues, diseased cells, or invading organisms. Included in the glycocalyx are cell-adhesion molecules that enable cells to adhere to each other and guide the movement of cells during embryonic development. The glycocalyx plays a major role in regulation of endothelial

vascular tissue Vascular tissue is a complex transporting tissue, formed of more than one cell type, found in vascular plants. The primary components of vascular tissue are the xylem and phloem. These two tissues transport fluid and nutrients internally. T ...

, including the modulation of red blood cell volume in capillaries. The term was initially applied to the polysaccharide matrix coating epithelial cells, but its functions have been discovered to go well beyond that.

In vascular endothelial tissue

The glycocalyx is located on the apical surface of vascular endothelial cells which line the lumen. When vessels are stained with cationic dyes such as Alcian blue stain,

transmission electron microscopy Transmission electron microscopy (TEM) is a microscopy technique in which a beam of electrons is transmitted through a specimen to form an image. The specimen is most often an ultrathin section less than 100 nm thick or a suspension on a g ...

shows a small, irregularly shaped layer extending approximately 50–100 nm into the lumen of a blood vessel. Another study used osmium tetroxide staining during freeze substitution, and showed that the endothelial glycocalyx could be up to 11 μm thick. It is present throughout a diverse range of microvascular beds (capillaries) and macrovessels (arteries and veins). The glycocalyx also consists of a wide range of enzymes and proteins that regulate leukocyte and thrombocyte adherence, since its principal role in the vasculature is to maintain plasma and vessel-wall homeostasis. These enzymes and proteins include: *Endothelial nitric oxide synthase ( endothelial NOS) *Extracellular superoxide dismutase ( SOD3) * Angiotensin converting enzyme * Antithrombin-III * Lipoprotein lipase * Apolipoproteins *

Growth factors A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regu ...

* Chemokines The enzymes and proteins listed above serve to reinforce the glycocalyx barrier against vascular and other diseases. Another main function of the glycocalyx within the vascular endothelium is that it shields the vascular walls from direct exposure to blood flow, while serving as a vascular permeability barrier. Its protective functions are universal throughout the vascular system, but its relative importance varies depending on its exact location in the vasculature. In microvascular tissue, the glycocalyx serves as a vascular permeability barrier by inhibiting coagulation and leukocyte adhesion. Leukocytes must not stick to the vascular wall because they are important components of the immune system that must be able to travel to a specific region of the body when needed. In arterial vascular tissue, the glycocalyx also inhibits coagulation and leukocyte adhesion, but through mediation of shear stress-induced nitric oxide release. Another protective function throughout the cardiovascular system is its ability to affect the filtration of interstitial fluid from capillaries into the interstitial space. The glycocalyx, which is located on the apical surface of endothelial cells, is composed of a negatively charged network of

proteoglycan Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to w ...

s, glycoproteins, and glycolipids. Along the luminal surface of the vascular glycocalyx exists an empty layer that excludes red blood cells.

Disruption and disease

Because the glycocalyx is so prominent throughout the cardiovascular system, disruption to this structure has detrimental effects that can cause disease. Certain stimuli that cause atheroma may lead to enhanced sensitivity of vasculature. Initial dysfunction of the glycocalyx can be caused by hyperglycemia or oxidized low-density lipoproteins ( LDLs), which then causes atherothrombosis. In microvasculature, dysfunction of the glycocalyx leads to internal fluid imbalance, and potentially edema. In arterial vascular tissue, glycocalyx disruption causes inflammation and atherothrombosis. Experiments have been performed to test precisely how the glycocalyx can be altered or damaged. One particular study used an isolated perfused heart model designed to facilitate detection of the state of the vascular barrier portion, and sought to cause insult-induced shedding of the glycocalyx to ascertain the cause-and-effect relationship between glycocalyx shedding and vascular permeability. Hypoxic perfusion of the glycocalyx was thought to be sufficient to initiate a degradation mechanism of the endothelial barrier. The study found that flow of oxygen throughout the blood vessels did not have to be completely absent ( ischemic hypoxia), but that minimal levels of oxygen were sufficient to cause the degradation. Shedding of the glycocalyx can be triggered by inflammatory stimuli, such as tumor necrosis factor-alpha. Whatever the stimulus is, however, shedding of the glycocalyx leads to a drastic increase in vascular permeability. Vascular walls being permeable is disadvantageous, since that would enable passage of some macromolecules or other harmful antigens. Other sources of damage to the endothelial glycocalyx have been observed in several pathological conditions such as inflammation, hyperglycemia, ischemia-reperfusion, viral infections and sepsis. Some key components of the glycocalyx such as syndecans, heparan sulphate, chondroitin sulphate and

hyaluronan Hyaluronic acid (; abbreviated HA; conjugate acid, conjugate base hyaluronate), also called hyaluronan, is an anion#Anions and cations, anionic, Sulfation, nonsulfated glycosaminoglycan distributed widely throughout connective tissue, connective ...

can be shed of the endothelial layer by enzymes. Hyaluronidase, hepararanse/heparinase, matrix and membrane-type matrix metalloproteases, thrombin, plasmin and elastase are some examples of enzymes that can induce shedding of the glycocalyx and these sheddases can therefor contribute to degradation of the glycocalyx layer in several pathological conditions. Research shows that plasma hyaluronidase activity is decreased in experimental as well as in clinical septic shock and is therefore not considered to be a sheddase in sepsis. Concomitant, the endogenous plasma inhibition of hyaluronidase is increased and could serve as a protection against glycocalyx shedding. Fluid shear stress is also a potential problem if the glycocalyx is degraded for any reason. This type of frictional stress is caused by the movement of viscous fluid (i.e. blood) along the lumen boundary. Another similar experiment was carried out to determine what kinds of stimuli cause fluid shear stress. The initial measurement was taken with intravital microscopy, which showed a slow-moving plasma layer, the glycocalyx, of 1 μm thick. Light dye damaged the glycocalyx minimally, but that small change increased capillary hematocrit. Thus, fluorescence light microscopy should not be used to study the glycocalyx because that particular method uses a dye. The glycocalyx can also be reduced in thickness when treated with oxidized LDL. These stimuli, along with many other factors, can cause damage to the delicate glycocalyx. These studies are evidence that the glycocalyx plays a crucial role in cardiovascular system health.

In bacteria and nature

A glycocalyx, literally meaning "sugar coat" (''glykys'' = sweet, ''kalyx'' = husk), is a network of

polysaccharide Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long-chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with wat ...

s that project from cellular surfaces of

, which classifies it as a universal surface component of a bacterial cell, found just outside the bacterial cell wall. A distinct, gelatinous glycocalyx is called a capsule, whereas an irregular, diffuse layer is called a slime layer. This coat is extremely hydrated and stains with ruthenium red. Bacteria growing in natural ecosystems, such as in soil, bovine intestines, or the human urinary tract, are surrounded by some sort of glycocalyx-enclosed microcolony. It serves to protect the bacterium from harmful phagocytes by creating capsules or allowing the bacterium to attach itself to inert surfaces, such as teeth or rocks, via

biofilm A biofilm is a Syntrophy, syntrophic Microbial consortium, community of microorganisms in which cell (biology), cells cell adhesion, stick to each other and often also to a surface. These adherent cells become embedded within a slimy ext ...

s (e.g. '' Streptococcus pneumoniae'' attaches itself to either lung cells,

prokaryotes A prokaryote (; less commonly spelled procaryote) is a single-celled organism whose cell lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Greek (), meaning 'before', and (), meaning 'nut' ...

, or other bacteria which can fuse their glycocalices to envelop the colony).

In the digestive tract

A glycocalyx can also be found on the apical portion of microvilli within the digestive tract, especially within the small intestine. It creates a meshwork 0.3 μm thick and consists of acidic mucopolysaccharides and glycoproteins that project from the apical plasma membrane of epithelial absorptive cells. It provides additional surface for adsorption and includes

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

s secreted by the absorptive cells that are essential for the final steps of digestion of proteins and sugars.

Other generalized functions

*Protection: Cushions the plasma membrane and protects it from chemical injury *Immunity to infection: Enables the immune system to recognize and selectively attack foreign organisms *Defense against cancer: Changes in the glycocalyx of

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

ous cells enable the immune system to recognize and destroy them. *Transplant compatibility: Forms the basis for compatibility of blood transfusions, tissue grafts, and organ transplants *Cell adhesion: Binds cells together so that tissues do not fall apart *Inflammation regulation: Glycocalyx coating on endothelial walls in blood vessels prevents leukocytes from rolling/binding in healthy states. *Fertilization: Enables

sperm Sperm (: sperm or sperms) is the male reproductive Cell (biology), cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm ...

to recognize and bind to eggs *Embryonic development: Guides embryonic cells to their destinations in the body

References

External links

Smart carbohydrate chemistry as a means to understand glycocalyx biology
– Video by the Lindhorst group at Beilstein TV {{Authority control Cell biology Polysaccharides Glycobiology Polymers