Understanding the extracellular vesicle surface for clinical molecular biology

Abstract

Extracellular vesicles (EVs) are lipid‐membrane enclosed nanoparticles that play significant roles in health and disease. EVs are abundant in body fluids and carry an array of molecules (proteins, lipids, nucleic acids and glycans) that reflect the identity and activity of their cell‐of‐origin. While the advent of high throughput omics technologies has allowed in‐depth characterisation of EV compositions, how these molecular species are spatially distributed within EV structures is not well appreciated. This is particularly true of the EV surface where a plethora of molecules are reported to be both integral and peripherally associated to the EV membrane. This coronal layer or ‘atmosphere’ that surrounds the EV membrane contributes to a large, highly interactive and dynamic surface area that is responsible for facilitating EV interactions with the extracellular environment. The EV coronal layer harbours surface molecules that reflect the identity of parent cells, which is likely a highly valuable property in the context of diagnostic liquid biopsies. In this review, we describe the current understanding of the mechanical, electrostatic and molecular properties of the EV surface that offer significant biomarker potential and contribute to a highly dynamic interactome.

Extracellular vesicles would be involved in the release and delivery of seminal TGF-β isoforms in pigs

“…Shelke et al (69) reported that TGF-β1 bound to EVs gives longer cell signaling over time compared to freely circulating TGF-β1. The present study demonstrated that a substantial part of the three TGF-β isoforms present in SP were bound to sEVs either as cargo inside, or outside in the so-called molecular corona surrounding the EVs (70), which plays a key role in the functional spectrum of EVs (71). Similar results were achieved by Fitzgerald et al (72) who reported that a substantial portion of several cytokines circulating in human blood plasma and amniotic fluid, TGF-βs among them, were bound to EVs, either inside or outside.…”

Extracellular Vesicles and Their Zeta Potential as Future Markers Associated with Nutrition and Molecular Biomarkers in Breast Cancer

“…The EVs membrane is a highly interactive and dynamic surface area that is responsible for facilitating EVs interactions with the extracellular environment [ 59 ]. It has been suggested that the interactions of small EVs act as modulators of signaling in biological processes, such as metastasis, cancer regulation, and tissue regeneration [ 60 ].…”

“…It has been suggested that the interactions of small EVs act as modulators of signaling in biological processes, such as metastasis, cancer regulation, and tissue regeneration [ 60 ]. Some of the mechanisms proposed to understand the interaction of EVs with other tissues are as follows: (1) fusion of the plasma membrane of EVs with the target cell, releasing its content inside; (2) vehicles of proteins and cellular components; upon arrival to the target cell, they can be fragmented by the action of proteases and act as a ligand for target cell receptors; and (3) endocytosis and pinocytosis [ 59 , 61 ]. Our results showed that the Zeta potential of EVs had several significant associations with clinical characteristics of the patients, as well as weight and visceral fat.…”

Potential of Mesenchymal Stromal Cell-Derived Extracellular Vesicles as Natural Nanocarriers: Concise Review

“…EV-based DDS present multiple advantages ( Figure 2 ): (1) their structure is composed of an aqueous core and a rich lipid bilayer surface structure, allowing for the compartmentalization and solubilization of both hydrophilic and lipophilic agents [ 59 ]. (2) EVs carry various biomolecules, such as proteins, lipids, and DNA and RNA species, depending on the producer cell types; the surface structure consists of fatty acids, high concentrations of cholesterol, sphingomyelin, ceramides, and other lipids; and interestingly, this surface also contains proteins that are implicated in adhesion, such as tetraspanins and αβ integrins, conferring on EVs an endogenous homing and targeting capacity [ 60 ]. (3) EVs are considered to be non-immunogenic, with a lower risk of allogeneic immune rejection from the host [ 61 ].…”