Biomechanical Properties of Blood Plasma Extracellular Vesicles Revealed by Atomic Force Microscopy

Abstract

While extracellular vesicles (EVs) are extensively studied by various practical applications in biomedicine, there is still little information on their biomechanical properties due to their nanoscale size. We identified isolated blood plasma vesicles that carried on biomarkers associated with exosomes and exomeres and applied atomic force microscopy (AFM) to study them at single particle level in air and in liquid. Air measurements of exosomes revealed a mechanically indented internal cavity in which highly adhesive sites were located. In contrast, the highly adhesive sites of exomeres were located at the periphery and the observed diameter of the particles was ~35 nm. In liquid, the reversible deformation of the internal cavity of exosomes was observed and a slightly deformed lipid bi-layer was identified. In contrast, exomeres were not deformed and their observed diameter was ~16 nm. The difference in diameters might be associated with a higher sorption of water film in air. The parameters we revealed correlated with the well-known structure and function for exosomes and were observed for exomeres for the first time. Our data provide a new insight into the biomechanical properties of nanoparticles and positioned AFM as an exclusive source of in situ information about their biophysical characteristics.

Perspectives of Microscopy Methods for Morphology Characterisation of Extracellular Vesicles from Human Biofluids

“…The measurements of the biomechanical properties revealed a soft internal cavity that was referred to as a disk-like shape, a stiffer membrane for exosome in the liquid and near-spherical shape in the air. By contrast, exomeres had similar heights in the air and the liquid environments [139]. EVs are considered promising biomarkers for thrombotic risk.…”

“…By contrast, EVs adsorbed to mica exhibit more or less roundly shaped morphology, even though, depending on the force applied with AFM tip, it is possible that some EVs, based on their intrinsic properties (stiffness, internal structure), also exhibit some irregular morphologies, including convex, planar or concave (cup-shaped). Nevertheless, the stiffer EVs remain almost completely spherical [139].…”

“…The force spectroscopy measurements of EVs are still scarcely studied. Bairamukov et al [139] found a correlation between the biomechanical properties of the EVs, their size, structure, and function. They used PeakForce QNM in air and liquid for measurements of exosomes and exomeres isolated by UC from blood plasma.…”

The application of mesenchymal stromal cells (MSCs) and their derivative exosome in skin wound healing: a comprehensive review

“…It is employed as a nanoscale mean to define the frequency, biomechanics, morphology, as well as biomolecular structure of exosome. This mean has the capability to estaimate samples in native circumstances with minimal provision [ 78 , 79 ].…”

Isolation of Cell-Free miRNA from Biological Fluids: Influencing Factors and Methods

“…[17,18,22,24,[27][28][29][30][31][32][33]] Specific microvesicles (prostasomes (50 nm-0.5 µm), melanosomes (>0.5 µm), 'platelet dust' (~130-500 nm)) [33][34][35][36][37] Membrane-free microparticles High-density lipoproteins (HDL) [23,[38][39][40][41][42] Low-density lipoproteins (LDL) [39,40,42] Various RNA-binding proteins (for example, AGO1, AGO2, nucleophosmin 1 (NPM1), Tamm-Horsfall protein (THP), etc.) [23,[43][44][45][46][47][48][49] Exomeres (~35 nm (<50 nm)) [50,51] miRNAs associated with the surface of blood cells [27,32]…”