Nucleated synthetic cells with genetically driven intercompartment communication

• 成果类型: Article
• 署名作者: Ioannou, Ion A.; Monck, Carolina; Ceroni, Francesca; Brooks, Nicholas J.; Kuimova, Marina K.; Elani, Yuval
• 署名单位: Imperial College London; Imperial College London; Imperial College London; Imperial College London
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12071
• DOI: 10.1073/pnas.2404790121
• 发表日期: 2024-09-03
• 关键词: staphylococcal alpha-hemolysin; beta-galactosidase; compartmentation; reconstitution; metabolism; origin

摘要

Eukaryotic cells are characterized by multiple chemically distinct compartments, one of the most notable being the nucleus. Within these compartments, there is a continuous exchange of information, chemicals, and signaling molecules, essential for coordinating and regulating cellular activities. One of the main goals of bottom-up synthetic biology is to enhance the complexity of synthetic cells by establishing functional compartmentalization. There is a need to mimic autonomous signaling between compartments, which in living cells, is often regulated at the genetic level within the nucleus. This advancement is key to unlocking the potential of synthetic cells as cell models and as microdevices in biotechnology. However, a technological bottleneck exists preventing the creation of synthetic cells with a defined nucleus- like compartment capable of genetically programmed intercompartment signaling events. Here, we present an approach for creating synthetic cells with distinct nucleus- like compartments that can encapsulate different biochemical mixtures in discrete compartments. Our system enables in situ protein expression of membrane proteins, enabling autonomous chemical communication between nuclear and cytoplasmic compartments, leading to downstream activation of enzymatic pathways within the cell.