Exploring lipid diversity and minimalism to define membrane requirements for synthetic cells.

The creation of minimal synthetic cells that mimic the essential functions of biological cells is a long-term goal in synthetic biology. Achieving this objective not only advances our understanding of the origin of life, but also unlocks the way for applications in industry, medicine, etc. A key characteristic of life is self-reproduction, which includes growth and division of the cell and its membrane. This boundary layer is formed by a lipid matrix in which proteins are anchored. The complexity of natural lipid membranes is a major challenge for the construction of a minimal system, as it directly influences membrane shape and protein function. Although simple synthetic compartmentalization systems can consist of a single lipid species, there is substantial uncertainty regarding the complexity of the lipidome required to sustain the essential functions of a self-reproducing cell. This Review highlights the contrast between bottom-up and top-down approaches toward synthetic cell construction, emphasizing the critical interplay between membrane proteins and their surrounding lipid environment. We explore the complexity and compatibility of membrane systems and discuss minimal lipidome requirements for synthetic cellular systems. Impact statement Synthetic cell research will help us to truly understand the basic principles of cellular life, in which lipid membranes are crucial. Ultimately, synthetic cells should lead to engineered specialized entities that can be applied in various fields, including medicine, bio-technology, and environmental science.