**Abstract**

Theoretical and experimental evidence on cellular vesicles (CVs) isolated from blood is presented. It is suggested that comparison of the observed shapes with theoretical shapes obtained by minimization of membrane-free energy in combination with electron microscopy is key in the assessment of CV identity. We found that shapes of CVs isolated from blood by repetitive centrifugation (up to 20.000 g) and washing, and observed by scanning electron microscopy (SEM) agreed well with theoretically observed shapes. It is indicated that these CVs are colloids deriving from residual blood cells, mostly platelets. SEM images of washed erythrocytes undergoing budding and transmission electron microscopy (TEM) images of isolated erythrocyte microvesicles likewise showed smooth shapes that we described as characteristic for colloidal CVs. Besides these, the CV isolates may contain other small particles, such as exosomes and viruses, as observed in isolates from tomato homogenate, however, we could not identify such particles in isolates from healthy human blood. Theory of deviatoric elasticity underlaying minimization of the membrane free energy and simulated two-component vesicles with the orientational ordering of anisotropic constituents are presented to indicate the interdependence of curvature—sorting of membrane constituents and their orientational ordering in strongly anisotropically curved regions.

**Keywords:** extracellular vesicles, erythrocyte microvesicles, extracellular vesicle shape, scanning electron images of extracellular vesicles; cryo-TEM images of extracellular vesicles
