Table of Contents
- Glycocalyx structure in Humans
- Glycocalyx Function in Humans
- Glycocalyx Functions in Bacteria
- Disruption of Glycocalyx
- Lesson Summary
Glycocalyx (sweet husk) was first described by Bennett HS in 1963 based on their polysaccharide composition of glycoproteins and glycolipids and later by Luft (1965) from the electron micrographs of microvessels. These are gel-like negatively charged filamentous structures are found on the luminal surface of blood vessels and act as molecular sieves controlling vascular homeostasis, inflammation, coagulation, and permeability. The glycocalyx comprises the scaffolding glycoproteins (mucins, selectins, adhesion molecules), glycosaminoglycans (Hyaluronan), and proteoglycans (heparin sulfate) associated with blood flow and blood components. Glycocalyx regulates the movement of fluids between the endothelial cells and functions as barriers to macromolecules. In addition to the filter function, the glycocalyx is involved in cell-cell recognition, adhesion, membrane bending, tabulation, and molding of the plasma membrane. Mucins are involved in tubulation and release of copious amounts of extracellular vesicles involved in carcinogenesis, tumor angiogenesis, and metastasis. Glycocalyx structural and functional defects lead to an inflammatory response in the blood vessels associated with vascular diseases including type 2 diabetes, atherosclerosis and sepsis.
The most contentious problem to date is to determine the exact shape, size, dynamics, and molecular interactions of glycocalyx due to its hydrophilic nature and lack of techniques. Vink E et al used intravital microscopy to follow the movement of red blood cells and fluorescent dextran in the plasma is filtered by the glycocalyx. In doing so, they identified a zone that was neither plasma nor red blood cells but extended into the endothelium. The size of this zone obtained by subtracting red blood cells and plasma zone from the fluorescent walls of the vessels is approx. 0.5 micron. Wheat germ agglutinin is used recently to follow the activities and structural modification of glycocalyx since it specifically binds to sugar molecules and allows the visualization of the entire glycocalyx architecture. The structure of glycocalyx is not yet fully elucidated. Based on the biochemical analysis, the glycocalyx is primarily composed of proteoglycans, glycosaminoglycans, and glycoproteins. The proteoglycans are either free-floating or attached with a long core and unbranched carbohydrate side chains and provide the backbone in the extracellular space.
The membrane-bound proteoglycans are attached to the cell membrane in two ways. First, by the syndecans of the single-span transmembrane domain. Then, the proteoglycans attach by their COOH terminus to the cell membrane through glycosylphosphotidylinositol (GPI) anchor (like Glypican). GPI anchors play a role in localizing protein to the luminal surface of the glycocalyx. The free-floating proteoglycans lack the transmembrane domains and are not connected to the cell membrane. However, they have strong interactions with the other components of the extracellular matrix like Perlecans, mimecan, decorin, versican, and biglycan). The perlecan's can bind to growth factors as well and help in activating the cells. The GAG's are long, linear polysaccharide molecules composed of repeating disaccharide units (heparan sulfate, chondroitin sulfate, dermatan sulfate, and Karastan sulfate). The most abundant and highly investigated GAG is heparin sulfate, accounting for 90% of endothelial cell proteoglycans and consisting of glucuronic acid and N-acetylglucosamine. Keratan sulfate consists of galacturonic acid and N-acetylglucosamine; chondroitin sulfate consists of glucuronic acid and N-acetylgalactosamine, and dermatan sulfate consists of glucuronic acid and N-acetylgalactosamine. These moieties undergo deacetylation and sulfation after the formation of the polysaccharide chain.
The glycoproteins differ from proteoglycans in having small branched carbohydrate side chains as opposed to long unbranched side chains. The adhesion molecules such as selectin, integrins, and immunoglobulins belong to the glycoprotein group. E-selectin and P-selectin are specific to endothelial cells and are overexpressed when endothelial cells are activated by inflammatory mediators. The integrins connect the extracellular matrix to the cytoskeleton and are involved in signal transduction. The intracellular adhesion molecule (ICAM's), platelet /endothelial cell adhesion molecule (PECAM-1), and vascular cell adhesion molecule (VCAM-1) belong to the immunoglobulin superfamily, which serves as ligands for growth factors and activates the intracellular signaling pathways.
Cobblestone-shaped endothelial cells form the inner lining of the blood vessels that are in angiogenesis, vasculogenesis, barrier functions, and tissue remodeling. The glycocalyx is found lining the endothelial cells and act as gatekeepers allowing movement of molecules and interacting with the components of the blood. Therefore, glycocalyx resides in the capillaries of almost all the vessels as endothelial cells occupy a vast surface area of all the vessels in the body. The heparan sulfate proteoglycans in the glycocalyx provide sites for plasma protein binding and hyaluronan binds to water molecules, conferring weight to the glycocalyx. Systemic glycocalyx volume, a measure of glycocalyx thickness varies with disease conditions wherein healthy glycocalyx is ~0.9um compared to ~0.5um in diabetes mellitus. The glycosaminoglycans provide support to the glycocalyx in the endothelium. The concentration of enzymes and growth factors is important to control the vascular tone. The endothelial glycocalyx acts as a control center, interacting with various proteins and enzymes like:
The gut luminal region is rich in microbial population and is exposed to mechanical forces of peristalsis. The enteric glycocalyx is composed primarily of mucins (MUC1, MUC3, MUC4, MUC12, MUC13, and MUC 17) protects the gut lumen, and serves as a host-microbe interface, and is important for the absorption of nutrients. Degradation of glycocalyx leads to numerous gastrointestinal diseases, including inflammatory bowel syndrome and cancer. Freeze etching and electron tomography show that enteric glycocalyx is a micrometer in length. In the small intestine, the glycocalyx is found on the epithelial cells and the lubricant mucus layer. They serve as receptors for intestinal flora to adhere and prevent pathogenic bacteria and viruses from entering the system. Glycocalyx also provides lubrication, protects against ulcers and autodigestion.
The glycocalyx is an active barrier performing key physiological functions depending on the cells, tissue, and location, such as
1. Vascular permeability
2. Clot formation
4. Mechanical transduction
5. Concentration of enzymes and factors
More recently, the glycocalyx is identified in the placenta at the maternal/fetal tissue interface. The placental syncytiotrophoblasts produce a glycocalyx, which is equivalent to the structure that is in contact with the maternal blood. Alterations in the endothelial glycocalyx structure and placental glycocalyx leads may lead to pre-eclampsia.
Similar to the eukaryotes, some of the bacteria secrete viscous polysaccharide glycocalyx or slime that protects them from dehydration and resists immune cells from phagocytosis or protozoans. The glycocalyx provides a mechanical barrier to antibiotics and is critical for the virulence of the bacteria. The glycocalyx may be tightly bound (capsules) or loosely bound (slime). The capsules prevent the bacteria from degradation and phagocytosis. Bacteria adhere to surfaces (teeth, hair, intestine) and colonize through the glycocalyx. Some of the components of bacterial glycocalyx such as peptidoglycan, teichoic acids, lipopolysaccharide, mannans, and glucans are found only in bacteria and not in humans. These pathogen-associated molecular patterns or PAMPs enable immune cells to recognize the bacteria and phagocytose the organisms. The capsules cover the C3b through opsonization to prevent engulfment by the phagocytes. Opsonization is a process by which opsonins, such as C3 and IgG, promote the attachment of the microbes to the immune cells and prevent the C3b receptor on phagocytes from recognizing C3b. Some of the examples of the bacteria that resist engulfment are Neisseria meningitidis, Streptococcus pneumoniae, Bacillus anthracis, Haemophilus influenzae type b, and Bordetella pertussis. The bacterial glycocalyx also functions as antigens and participates in the innate immune response.
The disintegration of glycocalyx compromises vascular integrity, causing edema, inflammation, and leakage of vascular components in the plasma. In addition, cell-cell adhesion, glycocalyx degradation also affect cell signaling, mechanotransduction, and membrane structures. The diseases associated with disruption of glycocalyx are sepsis, hypertension, cancer metastasis, type 2 diabetes, ischemia-reperfusion, and atherosclerosis.
Glycocalyx or the sweet hull of the cells is a protective layer separating the cells from the environmental stresses in both prokaryotes and eukaryotes. Primarily composed of glycoproteins, glycosaminoglycans, and proteoglycans, the glycocalyx is found lining the endothelial cells. It forms the entire vascular system responsible for oxygenation, delivery of nutrients, and removal of wastes. In addition to the selective permeability, the glycocalyx also acts as a lubricant, mechanotransducer, signaling hub, regulates complement activation, and participates in the innate immune response. Degradation of glycocalyx results in leakage of the plasma components, leukocytes extravasation, and alterations of vascular tone, and insufficient oxygenation and nutrition. Almost all vascular diseases, including hypertension, sepsis, type 2 diabetes, cancer, and atherosclerosis, are associated with a reduction of glycocalyx thickness.
To unlock this lesson you must be a Study.com Member.
Create your account
Glycocalyx regulates the movement of fluids between the endothelial cells and functions as barriers and prevents leakage of the plasma components. The disintegration of glycocalyx leads to increased permeability and loss of vascular integrity, thereby contributing to the disease phenotypes.
The main components of the glycocalyx are glycoproteins (mucins, selectins, adhesion molecules), glycosaminoglycans (Hyaluronan), and proteoglycans (heparin sulfate). They participate in various capacities to perform the glycocalyx functions.
The glycocalyx is the protective layer of the endothelial cells found on the lumen side of the vessels. The glycocalyx acts as a molecular sieve allowing only selective molecules to enter or leave the vessels. In the prokaryotes, the glycocalyx prevents recognition and destruction of the bacteria by the immune cells. Therefore, the glycocalyx is involved in maintaining vascular integrity and pathological conditions such as diabetes, sepsis, cancer are associated with reduction of the glycocalyx.
Already a member? Log InBack
I would definitely recommend Study.com to my colleagues. It’s like a teacher waved a magic wand and did the work for me. I feel like it’s a lifeline.