Researchers simulate behavior of living "minimal cell" in three dimensions

Scientists report that they have built a living “minimal cell” with a genome stripped down to its barest essentials and a computer model of the cell that mirrors its behavior. By refining and testing their model, the scientists are developing a system for predicting how changes to the genomes, living conditions, or physical characteristics of living cells will alter their function. The study was a collaboration between scientists from Illinois, Dresden, and California. The results were published in the journal Cell.

Minimal cells have reduced genomes that carry the genes necessary to replicate their DNA, grow, divide, and perform most of the other functions that define life. Scientists now developed a three-dimensional, fully dynamic computer model of a living minimal cell that mimics what goes on in the actual cell.

The simulation maps out the precise location and chemical characteristics of thousands of cellular components in three dimensional (3D) space at an atomic scale. It tracks how long it takes for these molecules to diffuse through the cell and encounter one another, what kinds of chemical reactions occur when they do, and how much energy is required for each step.

To build the minimal cell, scientists at the J. Craig Venter Institute (JCVI) in La Jolla, California turned to the simplest living cells, the mycoplasmas, a genus of bacteria that parasitize other organisms. In previous studies, the JCVI team built a synthetic genome missing as many nonessential genes as possible and grew the cell in an environment enriched with all the nutrients and factors needed to sustain it. For the new study, the team added back a few genes to improve the cell's viability. This cell is simpler than any naturally occurring cell, making it easier to model on a computer.

To build the computer model, the scientists had to account for the physical and chemical characteristics of the cell’s DNA, lipids, amino acids, gene-transcription, translation, and protein-building machinery. They also had to model how each component diffused through the cell, keeping track of the energy required for each step in the cell’s life cycle. The minimal cell simulations gave the researchers insight into how the actual cell balances the demands of its metabolism, genetic processes, and growth.

“The minimal cell is a perfect experimental platform to understand the design principles of living membranes,” says James Sáenz, research group leader at the B CUBE – Center for Molecular Engineering at TU Dresden, who contributed to this work together with his graduate student Nataliya Safronova. The group from Dresden provided the lipid composition for the minimal cell. This was the key to modeling how the cell surface area increases when the cell size increases.

The scientists simulated all of the chemical reactions inside a minimal cell – from its birth until the time it divides two hours later. From this, they got a model showing how the cell behaves and how the complexity can be increased to change the cell behavior.

“We are already following up on this work. We would like to see what is the exact role of lipids in determining the growth of function of the minimal cell,” explains Sáenz.

“Our model opens a window on the inner workings of the cell, showing us how all of the components interact and change in response to internal and external cues. This model – and other, more sophisticated models to come – will help us better understand the fundamental principles of life,” explains Zaida Luthey-Schulten, a chemistry professor at the University of Illinois Urbana-Champaign who led the work.

Publication
Zane R. Thornburg, David M. Bianchi, Troy A. Brier, Benjamin R. Gilbert, Tyler M. Earnest, Marcelo C.R. Melo, Nataliya Safronova, James P. Sáenz, Andra ́s T. Cook, Kim S. Wise, Clyde A. Hutchison III, Hamilton O. Smith, John I. Glass, and Zaida Luthey-Schulten: Fundamental behaviors emerge from simulations of a living minimal cell. Cell (January 2022)
Link: https://doi.org/10.1016/j.cell.2021.12.025

Media Contact
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