Nanomechanical probing of extracellular vesicles, liposomes and lipoproteins

Abstract

Mechanical characterization involves testing the hardness of various materials ranging from metals, plastics and composites to biological materials by application and measurement of load and deformation. While most of the above-mentioned materials are of larger sizes, biological systems often are submicrometer-sized, i.e. extracellular vesicles (EVs). EVs are small membrane-enclosed spheres secreted by cells and they are present in most of human body fluids. Despite their known roles, among others, in the creation of metastasis-favoring environments, and in intercellular communication, the knowledge about the mechanical properties of EVs is fairly limited, mainly because of their small size. Atomic force microscopy (AFM)-based nanoindentation - the method of choice in my thesis - allows for the mechanical characterization of single submicrometer-sized particles under close-to physiological environments. EVs in hereditary spherocytosis, the role of calcium-sensor proteins in membrane fusion, the function of tetraspanin CD63 in sorting cholesterol to HeLa-EVs as well as a potential effect of EV storage on their mechanical properties, inherent properties of lipoproteins (the main carriers of cholesterol and phospholipids within the human body) and the influence of oxygen on the mechanics of cervical cancer EVs were investigated. Next to better and deeper understanding of physiological processes within the human body, diseases and protein functions, mechanical characterization can drive forward the design of targeted drug delivery vehicles, and minimal-invasive diagnostics.