Synthetic Cell Aspirations: A Toolbox for Building a Membrane Container from the Bottom Up

Everything that we consider alive, be it plants, dogs, bacteria or humans, is composed of the same microscopic building blocks: cells. While cells between and even within these organisms can look and behave very differently, they all share the same key functionalities: they can grow, they can divide to proliferate, they can eat and metabolise to fuel internal processes, and they carry a genetic blueprint which they can process to knowwhat to do and how to do it. Since the first notion that cells formthe universal building blocks of life [1], biologists have been intrigued by the fact that across the wide diversity of living organisms, all these constituent cells share the same fundamental characteristics. In the process of understanding how cells are capable of executing the key functionalities of growth, division, metabolism and information processing, biologists have identified the set of molecular components that constitute cellular life, and have broadly related components to specific cell functions. Despite the growing knowledge on what there is inside the cell, a crucial question remains largely unanswered: how do the molecular components of a cell give rise to these life-giving processes? Answering that question that is easier said than done. Cells consist of thousands of different components that are in continuous interaction, can take over each other’s function, or have multiple functions. Extracting a mechanistic understanding of how these components actually work together to make the cell alive, is almost impossible in such a complex soup. Even if we can list the minimal set of components that are vital to cellular life, we gain little understanding in how these ingredients function to make non-living matter alive. Instead, for this purpose it might be more insightful to try to rebuild the cell with a minimal set of components: to build a synthetic cell. In such a bottom-up reconstitution approach, cell components and their interactions can be studied in a well-controlled chemical environment. Starting with a small number of components, complexity can step-by-step be increased while maintaining a fundamental understanding throughout the construction process. To achieve this goal of building a minimal cell, multiple research initiatives have been founded worldwide. As a unique interdisciplinary effort, synthetic cell research combines the expertise required to understand, rebuild and integrate all vital cellular functions in vitro...