SpudCell: The first synthetic cell with a complete cell cycle

Overview

Prof. Kate Adamala and her team at the University of Minnesota have built SpudCell, a cell-like system constructed entirely from known chemical components that can perform a complete cell cycle.

The system contains 36 purified enzymes, a 90,000 base pair genome spread across nine separate DNA molecules, and a lipid membrane. SpudCell is able to grow, replicate its genome, divide, and undergo selection and competition across multiple generations.

Unlike earlier work on minimal cells that carved down living cells, SpudCell is built entirely bottom-up from individually purified, non-living components. It is the first time such a system has demonstrated a complete cell cycle.

What SpudCell demonstrates

Genetically controlled feeding and growth. SpudCell grows by fusing with small “feeder liposomes” that deliver lipids for membrane growth plus nutrients including ribosomes, enzymes, and small molecules. Fusion happens when a protein that SpudCell makes from its own DNA locks onto the feeder’s membrane, with the cell’s DNA directly controlling whether it can feed, how fast it grows, and how large it becomes. Natural cells make their own nutrients through metabolism, which requires hundreds of genes encoding metabolic enzymes. By feeding externally instead, SpudCell can complete a full cell cycle with a much smaller genome.

SpudCell grows by fusing with small “feeder liposomes” that deliver lipids for membrane growth plus nutrients including ribosomes, enzymes, and small molecules. Fusion happens when a protein that SpudCell makes from its own DNA locks onto the feeder’s membrane, with the cell’s DNA directly controlling whether it can feed, how fast it grows, and how large it becomes. Natural cells make their own nutrients through metabolism, which requires hundreds of genes encoding metabolic enzymes. By feeding externally instead, SpudCell can complete a full cell cycle with a much smaller genome. Division without cytoskeleton. Natural cells divide using internal scaffolding called a cytoskeleton. Building a functional cytoskeleton from scratch has been a major bottleneck in synthetic cell research because it requires dozens of proteins working in coordination. SpudCell sidesteps this entirely, with proteins crowding together on the membrane surface until the mechanical stress makes the membrane split. Cells that make more of this surface protein divide more efficiently, directly coupling the genome to reproductive success.

Natural cells divide using internal scaffolding called a cytoskeleton. Building a functional cytoskeleton from scratch has been a major bottleneck in synthetic cell research because it requires dozens of proteins working in coordination. SpudCell sidesteps this entirely, with proteins crowding together on the membrane surface until the mechanical stress makes the membrane split. Cells that make more of this surface protein divide more efficiently, directly coupling the genome to reproductive success. Selection and competition. When researchers introduced a genetic change that increased production of the fusion protein, cells with that change grew faster and produced more offspring. After five generations, the faster-growing variant had outcompeted the original. Under nutrient scarcity, the advantage increased. This demonstrates selection and competition operating in a fully synthetic chemical system.

Breakdown of technical architecture

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