Design and Construction of Bottom-Up Synthetic Cells: From Minimal Life to Functional Biological Systems

Bottom-up synthetic biology represents one of the most dynamic frontiers of modern bioengineering, where the assembly of cell-like systems from molecular components is paving the way for the creation of minimal and functional biological entities. By integrating lipid vesicles, cell-free transcription–translation systems, genetic regulatory circuits, and energy-transducing modules, researchers are constructing synthetic cells capable of approximating, extending, or reimagining functions found in nature. These artificial systems provide unprecedented opportunities to test minimal-life hypotheses, explore the organisation of living matter, and engineer adaptive, autonomous behaviours. Recent advances include the development of protocells with encapsulated gene expression, light-driven energy production, programmable membrane functions, and synthetic–natural cell communication—milestones that redefine what it means to build life from the bottom up. However, considerable challenges remain, including achieving reproducibility in construction, enabling processes such as growth, division, and adaptation, and establishing predictable integration within biological or engineered environments. Continued interdisciplinary effort is critical to translate these conceptual breakthroughs into robust, controllable, and application-ready synthetic living systems.This Research Topic aims to highlight cutting-edge developments in the design, construction, and functionalisation of bottom-up synthetic cells, showcasing how artificial cellular systems are being engineered, characterised, and applied across biological and technological domains. By combining experimental, computational, and theoretical approaches, the Topic seeks to promote research that advances our ability to construct cellular architectures from molecular building blocks and achieve emergent functions such as energy metabolism, molecular communication, and information processing. Beyond their role as experimental mimics of life, bottom-up synthetic cells are positioned to become key tools for biotechnology, systems chemistry, and engineering—bridging the gap between living matter and programmable materials.To gather further insights into the evolving field of bottom-up synthetic biology, this Research Topic welcomes submissions aligned with the section’s scope—encompassing the molecular, informational, and systemic design principles that underpin artificial cellular systems. We invite articles addressing, but not limited to, the following themes:o Design, assembly, and characterization of liposome- or coacervate-based synthetic cellso Integration of cell-free expression and genetic regulation in artificial cellso Energy transduction mechanisms in photoautotrophic and chemiosmotic systemso Growth, division, self-replication, and adaptive functionality in synthetic cellso Molecular communication and interfacing between synthetic and living cellso Modeling, quantitative prediction, and control of emergent behavior in minimal systemso Development of synthetic-cell-based biomaterials, biosensors, and biotechnological platformso Theoretical, philosophical, and origins-of-life perspectives informing engineering design Topic editors: Pasquale Stano, Cheemeng Tan Source: https://www.frontiersin.org/research-topics/81978/design-and-construction-of-bottom-up-synthetic-cells-from-minimal-life-to-functional-biological-systems