Researchers at the University of Minnesota Twin Cities have developed a chemically defined synthetic cell system that can acquire resources, grow, replicate its genome, and divide. The cell-like system, called SpudCell, brings together functions that synthetic biologists have previously struggled to integrate within a single platform.
The researchers described SpudCell in a bioRxiv preprint. The study has not undergone peer review, and the system remains far from a self-sustaining living cell. However, integrating several life-like processes within a single chemically defined system represents an important advance for bottom-up synthetic biology.
Building a cell from nonliving components
Rather than modifying or simplifying an existing organism, the team assembled SpudCell from purified, nonliving components, including DNA, enzymes, ribosomes, and a lipid membrane. Its 90-kilobase genome is distributed across seven DNA plasmids that encode functions related to resource uptake, protein production, genome replication, growth, and division.
SpudCell receives resources by fusing with smaller lipid vesicles containing enzymes, ribosomes, and other materials. Genes within the synthetic cell direct the production of molecular tags that allow these feeder vesicles to attach to and merge with its membrane. This process supplies the materials the system needs to grow and copy its genome.
The researchers also developed a genetically encoded mechanism for division. Surface proteins accumulate on the membrane and interact with an added molecule, creating forces that can split the lipid compartment. This approach avoids the cytoskeleton-based machinery natural cells typically use to divide.
“This is likely the most exciting project I’ve ever worked on,” said Kate Adamala, associate professor in the University of Minnesota College of Biological Sciences. “We’ve replicated in chemistry what only used to be possible in biology: the complete set of behaviors of a cell.”
Selection without autonomous evolution
The researchers introduced a mutation that caused some SpudCells to produce more of the protein that captures feeder vesicles. Those variants acquired more resources, grew faster, and became more prevalent during repeated growth and division cycles.
The experiment demonstrated competition and selection within the system, but it did not represent autonomous Darwinian evolution. Researchers inserted the mutation themselves, and repeated division required mechanical assistance.
SpudCell also does not distribute its replicated DNA reliably between daughter compartments. After five division cycles, only 30 percent of the resulting cells retained the full genome. Its ribosomes degrade over time, and the system cannot produce replacements or independently remove damaged components.
A need for reproducible synthetic cell workflows
The project also illustrates the operational barriers laboratories face when developing complex synthetic biology platforms. Adamala said collaborators needed in-person demonstrations to reproduce some of the techniques, highlighting the difficulty of transferring methods that depend heavily on tacit knowledge.
The team identified shared protocols, modular components, and standardized synthetic cell platforms as priorities for future development. The researchers are also involved in Biotic, a public-benefit research organization intended to coordinate synthetic cell engineering and support open technical infrastructure.
For laboratories working in synthetic biology, the study demonstrates both the potential and the current fragility of bottom-up systems. Turning SpudCell into a reliable research or manufacturing platform will require more stable genome organization, improved division and inheritance, renewable molecular machinery, and workflows that laboratories can reproduce without extensive hands-on training.
“It’s inefficient, but you know exactly how it’s built,” Adamala said. That defined construction could allow researchers to improve individual components systematically, even as the system remains well short of a fully autonomous living cell.
This article was created with the assistance of Generative AI and has undergone editorial review before publishing.
