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One of the grand challenges in bottom-up synthetic biology is to build an artificial living cell from scratch. To achieve this, one requires an interdisciplinary approach which bridges biology, chemistry, materials science, artificial intelligence, and bridges length scales from molecules to cellular assembles to tissues. It has been widely recognized that life-like artificial cells should include features of compartmentalization, replication, metabolism, energization, adaptation, and evolutionary capacity. Integrating these features into artificial cells will not only give rise to possible solutions regarding the puzzle of the origin of life and provide minimal models for extant life, but also facilitate the development of new biological/chemical technologies and theories which bridge the gap between living and non-living matter. Significant progress has been demonstrated over the last decade, however, there still remains a limit in mimicking basic emergent cellular behavior. Achieving this goal requires the development of new and targeted methods which overcome challenges that arise from the hierarchical manipulation of soft materials with ever increasing molecular complexity. It is timely, for a special issue entitled “Artificial Cells” that will provide a unique platform to exchange new information and methods at the forefront of artificial cell research as well as highlighting future challenges for the artificial cell community. This special issue contains nine reviews and six research articles contributed from several esteemed experts in this research field, which not only discuss the past, present and future of artificial cell synthesis, but also present new techniques that advance the design and application of artificial cells. The construction of biomimetic soft compartments with life-like behavior is an emerging field. The reviews of Liangfei Tian and co-workers (2300422) and Xin Huang and co-workers (2201712) highlight the significance of structural complexity in artificial living systems. The former (2300422), from the perspective of spatial control, discusses various engineering strategies that can be used to precisely control the spatial positions within artificial systems. It raises an urgent requirement to expand the scope of the existing technology, such as 3D printing technology for the fabrication of populations of artificial cells. The latter (2201712) summarizes various multi-compartmentalized hierarchical systems and their different construction strategies. They focus on the sub-compartmentalization of synthetic cell (organelles) and the integration of synthetic cell communities (synthetic tissues) and emphasizes the important role of synthetic tissues in biomimetic materials in future. A further review contribution from Gijsje H. Koenderink, Kristina A. Ganzinger, and co-workers (2300416) focuses on different modes of production for giant unilamellar vesicles (GUV) with varying operational requirements. In another review contribution, Jean-Paul Douliez (2300530) discusses the formation of fatty acid protocells and vesicles from double emulsion methods. The research articles published in this special issue present new methods for the preparation of artificial cell models. Collin Nisler, Anna Wang, and co-workers (2300126) present a lipid exchange method to promote fusion of stable hemifused intermediates of fatty acid vesicles by adding vesicles made of different fatty acids to disturb lipid packing. Wenfeng Jiang, Yongfeng Zhou, and co-workers (2300136) develop a type of coacervate-assisted PISA (CAPISA) methodology to realize a one-pot and scalable preparation of hierarchical bi-shell capsules (BCs). The design of membrane-free coacervate droplets is important for the construction of artificial cell models with different physical properties. Nicolas Martin and co-workers (2300496) provide a focused review for the role of coacervate droplets as organelle-like modules and cytosol-like templates, including a discussion about their physicochemical properties and resulting bioinspired functions. The review by Evan Spruijt and co-workers (2300294) explores different ways in which coacervates and membranes can interact and discusses the subsequent structures that can arise from these interactions. What's more, the research article by Chen Chen, Tony Z. Jia, and co-workers (2300119) shows the physical characterization of salt-dependent dynamic phase behavior of polyester microdroplets by existing spectroscopic and biophysical methods. Increasing molecular complexity of artificial cell systems leads to increased functional diversity and there are several papers in this special issue which review or describe the incorporation of functions such as signaling, within synthetic cells. Stephen Mann, Hongjing Dou, and co-workers (2300231) review recent approaches involving invasive biochemical signals or non-invasive physical stimuli for signal transduction modules. Jianbo Liu and co-workers (2300042) provide an overview of the formation and design of coacervate-based artificial cell models, and discuss signaling communication strategies. Kwanwoo Shin and co-workers (2300182) focus on recent advances in the construction of controllable, self-regenerating artificial cells (SRACs), and the incorporation of dynamic properties is a step towards living cells. Finally, examples that focus on the emergence of new functionalities or applications artificial cell are presented. Dietmar Appelhans and co-workers (2300257) demonstrate the application of synthetic cells for capturing and digestion via the degradation A𝛽(1-40) peptide and protein pathogens. Neha P. Kamat and co-workers (2201718) demonstrate the use of cell-free expression systems to rapidly create protein-conjugated nanocarriers, bolstering the ability to create cell-mimetic therapeutics. Very interestingly, Petra Schwille and co-workers (2300173) asses the capability of MinDE proteins to drive patterns of biomedically-relevant molecules and high-order protein structures on membrane-coated 3D-printed micro swimmer-like structures and GUVs, showing the potential of spatially patterned functionalization of artificial biosystems. This special issue showcases the current state-of-the-art in the field of artificial cell synthesis and discusses the challenges and further perspectives from various angles. We hope to inspire more exciting research and discourse in this rapidly growing research field and hope that this special issue will encourage more interaction and collaborations among scientists across diverse disciplines. This will help to propel artificial cell research forward. We would like to thank all the authors for their exceptional contributions. We also extend our appreciation to Dr. Xi Wen, the editor-in-chief, as well as the other editors at Small Methods for their valuable support and commitment.
Tang et al. (Fri,) studied this question.