Nanotechnology & SynBio

Exploring Lipid Diversity And Minimalism To Define Membrane Requirements For Synthetic Cells

By Keith Cowing
Status Report
FEBS Letters
January 3, 2026
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Exploring Lipid Diversity And Minimalism To Define Membrane Requirements For Synthetic Cells
Schematic representation of key functions required for a synthetic minimal cell membrane. Integral and peripheral membrane proteins require a functional membrane environment that supports their structural integrity and enzymatic activity. The membrane serves as a key anchoring platform for the import of essential metabolites and the export of cellular products—both critical for maintaining physicochemical homeostasis. Among the fundamental characteristics of life are growth and division, processes that are tightly linked to lipid biosynthesis and membrane expansion. These functions cannot be sustained without continuous energy generation and regeneration, which in autonomous systems is typically driven by membrane-associated ion or proton gradients. Created with Inkscape (version 1.2.1). — FEBS Letters

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.

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