Systems of creation: the emergence of life from nonliving matter.

The advent of life from prebiotic origins remains a deep and possibly inexplicable scientific mystery. Nevertheless, the logic of living cells offers potential insights into an unknown world of autonomous minimal life forms (protocells). This Account reviews the key life criteria required for the development of protobiological systems. By adopting a systems-based perspective to delineate the notion of cellularity, we focus specific attention on core criteria, systems design, nanoscale phenomena and organizational logic. Complex processes of compartmentalization, replication, metabolism, energization, and evolution provide the framework for a universal biology that penetrates deep into the history of life on the Earth. However, the advent of protolife systems was most likely coextensive with reduced grades of cellularity in the form of simpler compartmentalization modules with basic autonomy and abridged systems functionalities (cells focused on specific functions such as metabolism or replication). In this regard, we discuss recent advances in the design, chemical construction, and operation of protocell models based on self-assembled phospholipid or fatty acid vesicles, self-organized inorganic nanoparticles, or spontaneous microphase separation of peptide/nucleotide membrane-free droplets. These studies represent a first step towards addressing how the transition from nonliving to living matter might be achieved in the laboratory. They also evaluate plausible scenarios of the origin of cellular life on the early Earth. Such an approach should also contribute significantly to the chemical construction of primitive artificial cells, small-scale bioreactors, and soft adaptive micromachines.