Nanomedicine, Volume I: Basic Capabilities

© 1999 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999 Vesicles, Granules, and Vaults

For most membranes, such as those of the Golgi complex and lysosomes, the transfer of manufactured lipid and protein from the rough ER occurs by means of 30-80 nm transport vesicles that pinch off from the rough ER and fuse with the target membranes. Some of these vesicles are coated with a bristlelike polyhedral lattice of clathrin subunits.3450,3451 Clathrin, a 180,000-dalton protein, is a distinctive feature of vesicles involved in a variety of intracellular transport processes. Besides bringing secretory proteins from the ER to the GC, clathrin-coated vesicles also transport membrane proteins from the GC to lysosomes (Section, to the plasma membrane (Section, and to other cellular destinations. In each case the clathrin coat forms a basket or cage around the vesicle, and transport involves cytoskeletal elements. Clathrins are cell specific -- for example, neuron clathrins have 12 pentagons and 20 hexagons, liver clathrins have 30 hexagons, and fibroblast clathrins have 60 hexagons and thus may be distinguished by medical nanorobots. In cultured cells, assembly of a free clathrin-coated vesicle takes ~1 minute, and >300-1000/min can be formed.3448,3449

Cellular products are concentrated and packaged before being discharged to the outside of the cell, a process known as exocytosis. Concentration occurs as structures called condensing vacuoles located on the periphery of the Golgi complex fill with concentrated protein, then fuse with one another to form larger secretory granules and vesicles. Outbound vesicles are given unique membrane compositions, including high-specificity targeting molecules that can bind only to receptor molecules located on the appropriate surface of the target acceptor compartments. A well-known example is the synaptic vesicle targeting protein synaptobrevin (VAMP 1 and 2) which binds only to the neuron-specific plasma membrane proteins syntaxin 1A and 1B, thus ensuring proper vesicle docking and fusion at the neuron cell plasma membrane.1079 In general, the fusion of two distinct lipid bilayers is energetically unfavorable in the absence of these specialized targeting proteins.

In some cells, the complementary process of endocytosis is also important.3452 In endocytosis, the cell ingests extracellular materials by invaginating the plasma membrane, then budding off vesicles, vacuoles (phagocytic, pinocytotic, etc.), or "endosomes" to the interior of the cell from these sites. Endocytosis and exocytosis produce opposite membrane flows, the former reducing plasma membrane mass and the latter increasing it via fusion. The net membrane flow can be rather large in cells that carry out both processes actively. For instance, in cultured macrophages an amount of membrane equivalent to the entire surface area of the cell is replaced in ~1800 sec, and macrophages may ingest ~25% of their volume per hour.996

Storage granules are also important in the cell. For example, glycogen is the storage polysaccharide of the animal body, also known as animal starch. It is a polymer of glucose. In many cells, large individual molecules of polymerized glucose measuring 10-40 nm in diameter appear as granules. The enzymes needed to carry out the synthesis and degradation of glycogen (including the synthetic enzyme glycogen synthase and the degradative enzyme glycogen phosphorylase) are bound to the surface of these glycogen granules in a ~5 nm-thick shell. These granules constitute up to 4-6% by weight of liver cells (~5 million granules), up to 0.7-1% of muscle cells, with lesser amounts in other cells (typically <105 granules) and only very small amounts in the brain, and are absent in some cells.

Another storage vesicle found floating in the cytoplasm is the lipid droplet containing triglyceride, the main storage form of fatty acids in cells. In many cells, these insoluble triglycerides coalesce in the cytosol to form large, anhydrous droplets from 0.2-5 microns in diameter. In adipocytes, the cells specialized for fat storage, these droplets can be as large as 80 microns, occupying virtually the entire cytosol and constituting up to ~99% of the cell's organic matter.938

Other intracellular storage vessels include melanin pigment granules found in certain cells of the skin and hairs; zymogen (enzyme-containing) granules synthesized in pancreatic cells, then transported into the small intestine; inflammatory toxins stored as intracellular granules in eosinophil leukocytes; ferritin molecules containing cellular iron stores (each ~610-690 kilodalton molecule is comprised of 24 subunits of 18,500 daltons each, which surround in an 8-nm-diameter-cavity micellar form some 3000-4500 ferric atoms);996,3380 and water vacuoles, mucus vesicles, and crystals of various types. The smallest observed effective hydrodynamic radius of sonicated phospholipid vesicles is ~10.25 nm independent of hydrocarbon chain length for synthetic even-numbered 12-18 carbon-chain phosphatidylcholines, and ~10.7 nm for egg-yolk phosphatidylcholine vesicles.2949

Finally, a related cell component is the vault, numbering in the thousands in human cells.3381 Vaults are barrel-shaped particles measuring ~55 nm x 30 nm, assembled from 96 copies of MVP (major vault protein) plus some integral RNA. Vaults look like pairs of unfolding flowers, each half having 8 petals attached to a central ring with a small hook. Vaults were first discovered in the mid-1980s and their exact function was not yet known in 1998. However, their structure suggested an ability to open and close as a natural part of their function in the cell,1410 and their size and shape would be an almost perfect match to dock at the nuclear pore complex3382 (Section, which suggested to some investigators that vaults might serve to ferry mRNA around the cell.1001,3381

In 1998, the chemical content of individual vesicles was analyzed regularly using a combination of optical trapping, capillary electrophoresis separation, and laser-induced fluorescence detection.1263


Last updated on 20 February 2003