was previously inseparably fused with all the rest of the world, set itself apart from the environment surrounding it." In this way, initial forms of self-organized systems may have acquired the capability to distinguish the in from the out, and later, the self from the nonself, traveling the path that eventually led to the smallest structural and functional unit of all living beings, the cell. [3] At a smaller scale, various cellular compartments and transmembrane cavities evolved to ensure the correct functioning, adaptation, and ultimately, the evolutionary capacity of the cell. The question is: "why spatial confinement should have been of advantage?" Possible answers rely on the fact that the physical segregation of chemical reactions within specialized compartments (or distinct phases) provides the possibility to enhance the local concentration of reactive species, separate the adducts from the products, prevent degradation of delicate compounds and limit contamination and/or competition from undesired chemicals. [4] Moreover, spatial coupling of local reactions may have favored nonlinear dynamics phenomena, such as, oscillations, feedback mechanisms, and complex spatiotemporal patterns, resulting in one of the most striking traits of living things, namely the emergence of complexity. [5] Compartmentalization is thus an essential feature of cellular life at all scales and is one of the strategies naturally evolved over billions of years to control biochemical reactions in space and time. [6] It is therefore not surprising that man-made reaction vessels have since decades inspired scientists, particularly from synthetic biology and systems chemistry, as ideal tools to mimic-and thus better understand-some central aspects of living matter. [7] Although several studies indicate that the core criteria required for the onset of synthetic cellularity might not necessitate the formation of membrane-delineated reaction volumes, the majority of natural compartments do indeed feature physical boundaries and these latter are often the result of a selfassembly process. Thus, besides the use of coacervates and microdroplets as membrane-less "phase-separation" tools, a large number of microenvironments have been reported, whose external shell is composed by the organized arrangement of lipids, polymeric amphiphilic molecules, inorganic nanoparticles, supramolecular metal complexes, protein units or nucleic acids. [8] The literature on this topic is too broad to be treated Compartmentalization is the strategy evolved by nature to control reactions in space and time. The ability to emulate this strategy through synthetic compartmentalization systems has rapidly evolved in the past years, accompanied by an increasing understanding of the effects of spatial confinement on the thermodynamic and kinetic properties of the guest molecules. DNA nanotechnology has played a pivotal role in this scientific endeavor and is still one of the most promising approaches for the construction of nanocompartments with programmable structur...
