Stiffness of natural extra-cellular vesicles is governed by membrane protein content

Extracellular vesicles (EVs) are important mediators of intercellular communication, being involved both in maintaining normal physiology as well as spreading of a wide range of diseases. In order to successfully deliver their cargo, EVs need to be taken up by the target cells. Several studies suggest that successful cellular uptake of nanoparticles is affected by their mechanical properties. We propose that mechanical properties of EVs are important with respect to their function. We study mechanics of vesicles from red blood cells (RBC), both healthy and malaria parasite infected. Moreover, we examine the effect of cell temperature treatment on the mechanical properties of the secreted vesicles. To do so we perform a detailed AFMforce spectroscopy study and analyze our results using a Helfrich-model based theoretical framework to estimate the bending modulus of different vesicle populations. By simultaneously performing a systematic analysis of EV protein and lipid composition, we find that bending modulus values are significantly decreased upon increase in EV membrane protein content. Our results can provide better understanding of EVs function and new insights into the vesiculation process in health and disease.