Recently, Stephen Mann, academician of the Royal Academy of Sciences, professor of the School of Materials Science and Engineering of Shanghai Jiaotong University and Professor of Zhangjiang Institute of Advanced Studies, published the research results entitled "Living material assembly of bacteriogenic protocells" online in the latest issue of the famous international journal Nature as a corresponding author. The research realized the generation of a prokaryotic cell-inspired eukaryotic cell bionic system based on the living material assembly of a single aggregate droplet for spatially controllable assembly and in-situ lysis of bacterial colonies, and achieved a major breakthrough in the research field of artificial cells.
The "reproduce" of similar functions of living cells in artificial cells is a global challenge that spans many fields including synthetic biology, bioengineering and the study of the origin of life. The traditional micro-compartmentalization method is difficult to establish enough composition diversity and biochemical complementarity in the artificial cell model, and its functionality is relatively single. How to solve the limitations of the current artificial cell models in the aspects of structural complexity and functional diversity and develop new bionic cell systems are the difficulties to be solved in the fields of artificial cells. In this study, the authors innovatively proposed a method based on polymer-adenosine triphosphate condensate droplets for spatially controlled assembly and in situ lysis of bacterial colonies, and successfully constructed artificial cells with membranes and complex molecular density, composition and morphology, and the first eukaryotic cell-like artificial cell based on prokaryotic cells was born. The work was extremely challenging and was conducted by postdoctoral fellow Can Xu under the guidance of Professor Stephen Mann. The co-corresponding author is Professor Mei Li.
In this study, they constructed the coacervate barrier as the structural skeleton of the artificial cells, and artificially reshaped bacteria based on their inheritance of different biological components. A three-dimensional network consisting of DNA-histone nuclear aggregates, membranous vesicles and F-actin cytoskeletal filaments was built inside the artificial cells. The results showed that F-actin, as a cytoskeletal protein, could undergo enzymatic polymerization in the "cytoplasm" of artificial cells to produce a filamentous network. While effectively improving the stability of the artificial cells, the research team was surprised to find that, with the accumulation of internal metabolites, the shape of the artificial cells gradually developed from the original spherical shape to an irregular amoeba-like cell shape. Moreover, while maintaining the complexity of the internal structure, the cell membrane of artificial cells can be continuously repaired by phospholipids derived from bacteria, thus greatly enhancing the sealing performance.
Figure 1. Construction of bacteriogenic protocells.
Figure 2. On-site augmentation of bacteriogenic protocells.
Figure 3. Live-cell-mediated morphogenesis in bacteriogenic protocells.
In this study, a novel artificial cell construction system based on prokaryotic cells was created for the first time, which not only provided design concepts and technical means for the construction of a eukaryotic cell bionic system with higher complexity, but also provided certain ideas and inspiration for scientific research in aspects such as the origin of life, and provided a good opportunity and platform for the cross integration and mutual development of multiple disciplines such as synthetic biology and bioengineering, with exciting research potential and development prospects.