Synthetic-Cell-Based Multi-Compartmentalized Hierarchical Systems

In the extant lifeforms, the self-sustaining behaviors refer to various well-organized biochemical reactions in spatial confinement, which rely on compartmentalization to integrate and coordinate the molecularly crowded intracellular environment and complicated reaction networks in living/synthetic cells. Therefore, the biological phenomenon of compartmentalization has become an essential theme in the field of synthetic cell engineering. Recent progress in the state-of-the-art of synthetic cells has indicated that multi-compartmentalized synthetic cells should be developed to obtain more advanced structures and functions. Herein, two ways of developing multi-compartmentalized hierarchical systems, namely interior compartmentalization of synthetic cells (organelles) and integration of synthetic cell communities (synthetic tissues), are summarized. Examples are provided for different construction strategies employed in the above-mentioned engineering ways, including spontaneous compartmentalization in vesicles, host-guest nesting, phase separation mediated multiphase, adhesion-mediated assembly, programmed arrays, and 3D printing. Apart from exhibiting advanced structures and functions, synthetic cells are also applied as biomimetic materials. Finally, key challenges and future directions regarding the development of multi-compartmentalized hierarchical systems are summarized; these are expected to lay the foundation for the creation of a "living" synthetic cell as well as provide a larger platform for developing new biomimetic materials in the future.