Synthetic cellularity based on non-lipid micro-compartments and protocell models

This review discusses recent advances in the design and construction of protocell models based on the self-assembly or microphase separation of non-lipid building blocks. We focus on strategies involving partially hydrophobic inorganic nanoparticles (colloidosomes), protein polymer globular nano-conjugates (proteinosomes), amphiphilic block copolymers (polymersomes), and stoichiometric mixtures of oppositely charged biomolecules and polyelectrolytes (coacervates). Developments in the engineering of membrane functionality to produce synthetic protocells with gated responses and control over multi-step reactions are described. New routes to protocells comprising molecularly crowded, cytoskeletal-like hydrogel interiors, as well as to the construction of hybrid protocell models are also highlighted. Together, these strategies enable a wide range of biomolecular and synthetic components to be encapsulated, regulated and processed within the micro-compartmentalized volume, and suggest that the development of non-lipid micro-ensembles offers an approach that is complementary to protocell models based on phospholipid or fatty acid vesicles.