Extracellular Vesicles

What are Extracellular Vesicles?

Extracellular vesicles (EVs) are small, membrane-bound particles which found in both eukaryotes (include animals, plants and protist) and prokaryotes (include bacteria and archaea).  They are present in biological fluids such as saliva, urine, breast milk and plasma. EVs are involved in multiple physiological and pathological processes.  EVs are like cell to cell messengers which play critical functions in intercellular communication by allowing cells to exchange messages such as proteins, lipids and genetic materials.  Several types of EVs are produced by normal healthy cells and diseased cells.  Therefore, there has been an extensive expansion in the research of using EVs to further study the pathogenesis of diseases and discover potential diagnostic tools such as biomarkers that could identify and distinguish diseases, as well as develop suitable treatments for patients.  

The general structure and different types of EVs

Extracellular vesicles consist of lipid bilayer membranes which is similar to cell plasma membrane.  The membranes comprise lipid such as Sphingomyelin, cholesterol, ceramics, and phosphatidylserine.  EVs contain various metabolites such as amino acids, tricarboxylic acid cycle (TCA) intermediates.  Also, EVs have cytoplasmic proteins and transmembrane proteins such as cytokines, metabolic enzymes, ribosomal proteins, targeting or adhesion molecules, and antigen presentation.  There are different types of EVs and the nomenclature depends on their ways of biogenesis and where they originate from.

(Figure from Chulpanova et al., 2018)

EVs can be classified into three classes: microvesicles, exosomes and apoptotic bodies.  Each class of EVs has a specific mechanism of synthesis, and within each class, different subtypes can be distinguished by their distinct proteins and RNA signatures.

How small are the EVs?

Extracellular vesicles are tiny and measured in nanometers which are an incredibly small scale. To illustrate how small the extracellular vesicles are, if we blow a one penny (20mm) up to the size of the Earth (12,742km), and compare it to some smaller things in the world. The diameter of an exosome (50-100 nm) would be the height of the Tower Bridge in London (65m). Working up our scales, a microvesicle (100-1000 nm) would be the height of Shanghai Tower (632m). And an apoptotic body (50nm-2μm) would be the height of the Mount Wellington in Tasmania (1,271m).

The functions and biogenesis of different EVs

The biogenesis of extracellular vesicles varies depending on their classes.

Exosomes are known for intercellular communication in both normal and diseases tissue and its biogenesis starts within the endosomal system and the release of exosome involved several cellular steps. These include:

  1. formation of intracellular vesicles which carry materials from the cell surface and the extracellular space, to the
  2. fusion of intracellular vesicle to the early endosome
  3. formation of intraluminal vesicles (ILVs) with various types of cargos sorted inside them (in this stage they are known as multivesicular body, MVB)
  4. followed by transport and fusion of MVBs with plasma membrane by exocytosis which then lead to the release of vesicles known as exosomes

Microvesicles is are also known for intercellular communication of many processes, including regulation of programmed cell death, modulation of the immune response, inflammation, angiogenesis and coagulation. Unlike the exosomes, its formation involves both redistribution of membrane lipids and vertical trafficking of molecular cargo to the plasma membrane. Microvesicles formation involves the outward budding of plasma membrane which then pinches off with its cargo loaded into the microvesicles as it forms.

Apoptotic body is used to facilitate phagocytosis and it is formed only during programmed cell death. When a cell die, it initiate condensation of the nuclear chromatin followed by membrane blebbing. The disintegration of the cellular content then leads to distinct membrane enclosed vesicles known as apoptotic body.