Vesicle (biology and chemistry)

Scheme of a liposome formed by phospholipids in an aqueous solution.

In cell biology, a vesicle is a small structure within a cell, consisting of fluid enclosed by a lipid bilayer. Vesicles form naturally during the processes of secretion (exocytosis), uptake (phagocytosis and endocytosis) and transport of materials within the cytoplasm. Alternatively, they may be prepared artificially, in which case they are called liposomes. If there is only one phospholipid bilayer, they are called unilamellar liposome vesicles; otherwise they are called multilamellar. The membrane enclosing the vesicle is also a lamellar phase, similar to that of the plasma membrane, and vesicles can fuse with the plasma membrane to release their contents outside the cell. Vesicles can also fuse with other organelles within the cell.

Vesicles perform a variety of functions. Because it is separated from the cytosol, the inside of the vesicle can be made to be different from the cytosolic environment. For this reason, vesicles are a basic tool used by the cell for organizing cellular substances. Vesicles are involved in metabolism, transport, buoyancy control,^[1] and enzyme storage. They can also act as chemical reaction chambers.

Sarfus image of lipid vesicles.

IUPAC definition

Closed structure formed by amphiphilic molecules that contains solvent (usually water).^[2]

The 2013 Nobel Prize in Physiology or Medicine was shared by James Rothman, Randy Schekman, and Thomas Südhof for their roles (building upon earlier research, some of it by their mentors) on the makeup and function of cell vesicles, especially in yeasts and in humans, including information on each vesicle's parts and how they are assembled. When cell vesicles, which help maintain a balance or equilibrium inside and outside of the blood vessels and cells (between the intravascular and extravascular spaces and the intracellular and extracellular spaces, respectively), malfunction, potentially serious and often fatal conditions are the result. The dysfunction is thought to contribute to Alzheimer's disease, diabetes, some hard-to-treat cases of epilepsy, some cancers and immunological disorders, and certain neurovascular conditions. These are likely either caused, influenced, or made worse, by the disorders of the cell vesicles.^[3][4]

Types of Vesicles

Electron micrograph of a cell containing a food vacuole (fv) and transport vacuole (TV) in a malaria parasite.

Vacuoles

Vacuoles are vesicles which contain mostly water.

• Plant cells have a large central vacuole in the center of the cell that is used for osmotic control and nutrient storage.
• Contractile vacuoles are found in certain protists, especially those in Phylum Ciliophora. These vacuoles take water from the cytoplasm and excrete it from the cell to avoid bursting due to osmotic pressure.

Lysosomes

• Lysosomes are involved in cellular digestion. Food can be taken from outside the cell into food vacuoles by a process called endocytosis. These food vacuoles fuse with lysosomes which break down the components so that they can be used in the cell. This form of cellular eating is called phagocytosis.
• Lysosomes are also used to destroy defective or damaged organelles in a process called autophagy. They fuse with the membrane of the damaged organelle, digesting it.

Transport vesicles

• Transport vesicles can move molecules between locations inside the cell, e.g., proteins from the rough endoplasmic reticulum to the Golgi apparatus.
• Membrane-bound and secreted proteins are made on ribosomes found in the rough endoplasmic reticulum. Most of these proteins mature in the Golgi apparatus before going to their final destination which may be to lysosomes, peroxisomes, or outside of the cell. These proteins travel within the cell inside of transport vesicles.

Secretory vesicles

Secretory vesicles contain materials that are to be excreted from the cell. Cells have many reasons to excrete materials. One reason is to dispose of wastes. Another reason is tied to the function of the cell. Within a larger organism, some cells are specialized to produce certain chemicals. These chemicals are stored in secretory vesicles and released when needed.

Types of secretory vesicles

• Synaptic vesicles are located at presynaptic terminals in neurons and store neurotransmitters. When a signal comes down an axon, the synaptic vesicles fuse with the cell membrane releasing the neurotransmitter so that it can be detected by receptor molecules on the next nerve cell.
• In animals endocrine tissues release hormones into the bloodstream. These hormones are stored within secretory vesicles. A good example is the endocrine tissue found in the islets of Langerhans in the pancreas. This tissue contains many cell types that are defined by which hormones they produce.
• Secretory vesicles hold the enzymes that are used to make the cell walls of plants, protists, fungi, bacteria, and Archaea cells as well as the extracellular matrix of animal cells.
• Bacteria, Archaea, fungi, and parasites release membrane vesicles (MVs) containing varied but specialized toxic compounds and biochemical signal molecules, which are transported to target cells to initiate processes in favour of the microbe, which include invasion of host cells and killing of competing microbes in the same niche.^[5]

Extracellular vesicles

Extracellular vesicles (EVs) are produced by all domains of life including complex eukaryotes, both Gram-negative and Gram-positive bacteria, mycobacteria, and fungi. Nomenclature exists for a variety of extracellular vesicle types including :

• exosomes: membraneous vesicles of endocytic origin (50-100 nm diameter)^{[6]:Table 1} enriched in CD63 and CD81.^[6]
• microvesicle (also referred to as shedding microvesicles, SMVs), that are shed directly from the plasma membrane, (20-1000 nm^{[6]:Table 1} )
• membrane particles, (50-80 nm), or large membranous vesicles (~600 nm) CD133⁺, CD63^-[6]
• apoptotic blebs or vesicles (1000-5000 nm diameter): released by dying cells.^{[6]:Table 1}

These are often separated by density^{[6]:Table 1} by differential centrifugation.

Ectosomes were named in 2008, but in 2012 are not considered a separate type.^[6]

In humans, endogenous extracellular vesicles likely play a role in coagulation, intercellular signaling, and waste management.^[6]

In Gram-negative bacteria, EVs are produced by the pinching off of the outer membrane; however, how EVs escape the thick cell walls of Gram-positive bacteria, mycobacteria and fungi is still unknown. These EVs contain varied cargo, including nucleic acids, toxins, lipoproteins and enzymes, and have important roles in microbial physiology and pathogenesis. In host-pathogen interactions, gram negative bacteria produce vesicles which play roles in establishing a colonization niche, carrying and transmitting virulence factors into host cells, and modulating host defense and response.^[7]

Ocean cyanobacteria have been found to continuously release vesicles containing proteins, DNA, and RNA into the open ocean. Vesicles carrying DNA from diverse bacteria are abundant in coastal and open-ocean seawater samples.^[8]

Other types of vesicles

Main article: Gas vesicle

Gas vesicles are used by Archaea, bacteria and planktonic microorganisms, possibly to control vertical migration by regulating the gas content and thereby buoyancy, or possibly to position the cell for maximum solar light harvesting. These vesicles are typically cylindrical tubes made out of protein; their diameter determines the strength of the vesicle with larger ones being weaker. The diameter of the vesicle also affects it's volume and how efficiently it can provide buoyancy. In cyanobacteria natural selection has worked to create vesicles that are at the maximum diameter possible while still being structurally stable. The protein skin is permeable to gasses but not water, keeping the vesicles from flooding.^[9]

Matrix vesicles are located within the extracellular space, or matrix. Using electron microscopy they were discovered independently in 1967 by H. Clarke Anderson^[10] and Ermanno Bonucci.^[11] These cell-derived vesicles are specialized to initiate biomineralisation of the matrix in a variety of tissues, including bone, cartilage, and dentin. During normal calcification, a major influx of calcium and phosphate ions into the cells accompanies cellular apoptosis (genetically determined self-destruction) and matrix vesicle formation. Calcium-loading also leads to formation of phosphatidylserine:calcium:phosphate complexes in the plasma membrane mediated in part by a protein called annexins. Matrix vesicles bud from the plasma membrane at sites of interaction with the extracellular matrix. Thus, matrix vesicles convey to the extracellular matrix calcium, phosphate, lipids and the annexins which act to nucleate mineral formation. These processes are precisely coordinated to bring about, at the proper place and time, mineralization of the tissue's matrix unless the Golgi are non-existent.

Multivesicular body, or MVB, is a membrane-bound vesicle containing a number of smaller vesicles.

Vesicle formation and transport

Cell biology
The animal cell
Components of a typical animal cell: Nucleolus Nucleus Ribosome (little dots) Vesicle Rough endoplasmic reticulum Golgi apparatus (or "Golgi body") Cytoskeleton Smooth endoplasmic reticulum Mitochondrion Vacuole Cytosol (fluid that contains organelles) Lysosome Centrosome Cell membrane

Some vesicles are made when part of the membrane pinches off the endoplasmic reticulum or the Golgi complex. Others are made when an object outside of the cell is surrounded by the cell membrane.

Capturing cargo molecules

The assembly of vesicles requires numerous coats to surround and bind to the proteins being transported; these bind to the coat vesicle. They also trap various transmembrane receptor proteins, called cargo receptors, which in turn trap the cargo molecules.

Vesicle coat

The vesicle coat serves to sculpt the curvature of a donor membrane, and to select specific proteins as cargo. It selects cargo proteins by binding to sorting signals. In this way the vesicle coat clusters selected membrane cargo proteins into nascent vesicle buds.

There are three types of vesicle coats: clathrin, COPI, and COPII. Clathrin coats are found on vesicles trafficking between the Golgi and plasma membrane, the Golgi and endosomes, and the plasma membrane and endosomes. COPI coated vesicles are responsible for retrograde transport from the Golgi to the ER, while COPII coated vesicles are responsible for anterograde transport from the ER to the Golgi.

The clathrin coat is thought to assemble in response to regulatory G protein. A coatomer coat assembles and disassembles due to an ADP ribosylation factor (ARF) protein.

Vesicle docking

Surface markers called SNAREs identify the vesicle's cargo, and complementary SNAREs on the target membrane act to cause fusion of the vesicle and target membrane. Such v-SNARES are hypothesised to exist on the vesicle membrane, while the complementary ones on the target membrane are known as t-SNAREs.

Often SNAREs associated with vesicles or target membranes are instead classified as Qa, Qb, Qc, or R SNAREs owing to further variation than simply v- or t-SNAREs. An array of different SNARE complexes can be seen in different tissues and subcellular compartments, with 36 isoforms currently identified in humans.

Regulatory Rab proteins are thought to inspect the joining of the SNAREs. Rab protein is a regulatory GTP-binding protein, and controls the binding of these complementary SNAREs for a long enough time for the Rab protein to hydrolyse its bound GTP and lock the vesicle onto the membrane.

Vesicle fusion

Vesicle fusion can occur in one of two ways: full fusion or kiss-and-run fusion. Fusion requires the two membranes to be brought within 1.5 nm of each other. For this to occur water must be displaced from the surface of the vesicle membrane. This is energetically unfavorable, and evidence suggests that the process requires ATP, GTP, and acetyl-coA. Fusion is also linked to budding, which is why the term budding and fusing arises.

Vesicles in receptor downregulation

Membrane proteins serving as receptors are sometimes tagged for downregulation by the attachment of ubiquitin. After arriving an endosome via the pathway described above, vesicles begin to form inside the endosome, taking with them the membrane proteins meant for degradation; When the endosome either matures to become a lysosome or is united with one, the vesicles are completely degraded. Without this mechanism, only the extracellular part of the membrane proteins would reach the lumen of the lysosome, and only this part would be degraded.^[12]

It is because of these vesicles that the endosome is sometimes known as a multivesicular body. The pathway to their formation is not completely understood; unlike the other vesicles described above, the outer surface of the vesicles is not in contact with the cytosol.

Vesicle preparation

Isolated vesicles

Producing membrane vesicles is one of the methods to investigate various membranes of the cell. After the living tissue is crushed into suspension, various membranes form tiny closed bubbles. Big fragments of the crushed cells can be discarded by low-speed centrifugation, and later the fraction of the known origin (plasmalemma, tonoplast, etc.) can be isolated by precise high-speed centrifugation in the density gradient. Using osmotic shock, it is possible temporarily open vesicles (filling them with the required solution) and then centrifugate down again and resuspend in a different solution. Applying ionophores like valinomycin can create electrochemical gradients comparable to the gradients inside living cells.

Vesicles are mainly used in two types of research:

• To find and later isolate membrane receptors that specifically bind hormones and various other important substances.^[13]
• To investigate transport of various ions or other substances across the membrane of the given type.^[14] While transport can be more easily investigated with patch clamp techniques, vesicles can also be isolated from objects for which a patch clamp is not applicable.

Artificial vesicles

Phospholipid vesicles have also been studied in biochemistry. For such studies, a homogeneous phospholipid vesicle suspension can be prepared by sonication,^[15] injection of a phospholipid solution into the aqueous buffer solution membranes.^[16] In this way aqueous vesicle solutions can be prepared of different phospholipid composition, as well as different sizes of vesicles.

See also

• Bleb (cell biology)
• DODAB
• Membrane contact sites
• Membrane nanotube
• Micelle
• Protocell
• Spitzenkörper, a structure of many small vesicles found in fungal hyphae
• Membrane vesicle trafficking
• Host-pathogen interface

References

1. Walsby AE (1994). "Gas vesicles". Microbiological reviews 58 (1): 94–144. PMC 372955. PMID 8177173.
2. "Terminology of polymers and polymerization processes in dispersed systems (IUPAC Recommendations 2011)" (PDF). Pure and Applied Chemistry 83 (12): 2229–2259. 2011. doi:10.1351/PAC-REC-10-06-03.
3. "Nobel medical prize goes to 2 Americans, 1 German". CNN. 2005-10-19. Retrieved 2013-10-09.
4. 2013 Nobel Prize in Physiology or Medicine, press release 2013-10-07
5. Deatherage, B. L.; Cookson, B. T. (2012). "Membrane Vesicle Release in Bacteria, Eukaryotes, and Archaea: a Conserved yet Underappreciated Aspect of Microbial Life". Infection and Immunity 80 (6): 1948–1957. doi:10.1128/IAI.06014-11. ISSN 0019-9567.
6. van der Pol, Edwin; Böing, Anita N.; Harrison, Paul; Sturk, Augueste; Nieuwland, Rienk (2012-07-01). "Classification, functions, and clinical relevance of extracellular vesicles". Pharmacological Reviews 64 (3): 676–705. doi:10.1124/pr.112.005983. ISSN 1521-0081. PMID 22722893. Free full text
7. Kuehn, Meta J.; Kesty, Nicole C. (2005-11-15). "Bacterial outer membrane vesicles and the host-pathogen interaction". Genes & Development 19 (22): 2645–2655. doi:10.1101/gad.1299905. ISSN 0890-9369. PMID 16291643.
8. Biller, Steven J.; Schubotz, Florence; Roggensack, Sara E; Thompson, Anne W.; Summons, Roger E.; Chisholm, Sallie W. (2014-01-10). "Bacterial Vesicles in Marine Ecosystems". Science 343 (6167): 183–186. doi:10.1126/science.1243457. ISSN 0036-8075. PMID 24408433.
9. Walsby, Anthony (March 1994). "Gas Vesicles" (PDF). Microbiological Reviews. Retrieved Jan 29, 2016.
10. Anderson HC (1967). "Electron microscopic studies of induced cartilage development and calcification". J. Cell Biol. 35 (1): 81–101. doi:10.1083/jcb.35.1.81. PMC 2107116. PMID 6061727.
11. Bonucci E (1967). "Fine structure of early cartilage calcification". J. Ultrastruct. Res. 20 (1): 33–50. doi:10.1016/S0022-5320(67)80034-0. PMID 4195919.
12. Katzmann DJ, Odorizzi G, Emr SD (2002). "Receptor downregulation and multivesicular-body sorting" (PDF). Nat. Rev. Mol. Cell Biol. 3 (12): 893–905. doi:10.1038/nrm973. PMID 12461556.
13. Sidhu VK, Vorhölter FJ, Niehaus K, Watt SA (2008). "Analysis of outer membrane vesicle associated proteins isolated from the plant pathogenic bacterium Xanthomonas campestris pv. campestris". BMC Microbiol. 8: 87. doi:10.1186/1471-2180-8-87. PMC 2438364. PMID 18518965.
14. Scherer GG, Martiny-Baron G (1985). "K+
    /H+
    exchange transport in plantmembranevesicles is evidence for K+
    transport". Plant Science 41 (3): 161–8. doi:10.1016/0168-9452(85)90083-4.
15. Barenholz, Y.; Gibbes, D.; Litman, B. J.; Goll, J.; Thompson, T. E.; Carlson, F. D. (1977). "A simple method for the preparation of homogeneous phospholipid vesicles". Biochemistry 16 (12): 2806–10. doi:10.1021/bi00631a035. PMID 889789.
16. Batzri S, Korn ED (April 1973). "Single bilayer liposomes prepared without sonication". Biochim. Biophys. Acta 298 (4): 1015–9. doi:10.1016/0005-2736(73)90408-2. PMID 4738145.

Further reading

• Alberts, Bruce; et al. (1998). Molecular Biology of the Cell (Fourth ed.). New York: Garland. ISBN 0-8153-2971-7.

External links

• Lipids, Membranes and Vesicle Trafficking - The Virtual Library of Biochemistry and Cell Biology