Chapter 1 10 The wide wealthy world of communication The living world is a collection of ecosystems in which the interactions between individual components determine the emergent properties of complex biological systems 1. Such interactions are mainly driven through communication between or within species and organisms, which are subject to changing environmental conditions. As such, the state of a system is reflected by its occupying species, which may be studied to infer environmental changes. To illustrate: bees are considered an indicator species meaning that their vibrancy on earth reflects environmental conditions and aids in gauging the health of ecosystems. Simply put, reduced numbers of bees in a given hive indicate a decline in environmental conditions. Similar to studying bees to infer environmental status, studying biomolecules released by cells – as means of intercellular communication – allows researchers to infer cellular status, and, by extension, the status of cellular systems as a whole. This is of paramount importance in the context of health and disease. Broadly speaking, cellular communication is performed through either direct contact with neighboring cells or the excretion of biomolecules into the extracellular space. A relatively recently discovered and exciting modality of such an excreted means of communication, and the subject of this thesis, are extracellular vesicles (EVs). A brief history of EV-erything EVs were first described in a series of manuscripts which identified potential structures that would retrospectively be described as EVs 2. In 1946, Chargaff and West reported the discovery of a ‘particulate fraction’ which sedimented from human plasma at 31,000 g (but remained at solution at 5,000 g). At the time, these particles were suggested to be a form of cellular waste 3. In 1967, Peter Wolf described a “material in minute form, sedimentable by high-speed centrifugation and originating from platelets, but distinguishable from intact platelets” – which we now know as the EV fraction. Wolf provided electron microscopy images of these particles, which he described as ‘platelet dust’ 4. A few years later (1971), Neville Crawford published further images of these particles – which were now being described as ‘microparticles’ – and showed that these particles contained lipids and carried cargo such as the cellular energy source adenosine triphosphate (ATP) 5, thus suggesting that these particles were more than cellular debris or waste particles. These pioneering experiments were the first to describe the presence and structure of such cell-free components and hinted at their potential biological importance.
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