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Artificial cells show why crowding is key

CARNEGIE MELLON (US) — Gene expression goes better in tight quarters, especially when other conditions are less than ideal, say researchers.

As the researchers report in an advance online publication in Nature Nanotechnology, these findings may help explain how cells have adapted to the phenomenon of molecular crowding, which has been preserved through evolution.

And this understanding may guide synthetic biologists as they develop artificial cells that might someday be used for drug delivery, biofuel production, and biosensors.

“These are baby steps we’re taking in learning how to make artificial cells,” says study leader Cheemeng Tan, a postdoctoral fellow in the Lane Center for Computational Biology at Carnegie Mellon University.

The findings could guide synthetic biologists as they develop artificial cells that might someday be used for drug delivery, biofuel production and biosensors. Above, artificial cells used in the study. (Credit: Carnegie Mellon)

Most studies of synthetic biological systems today employ solution-based chemistry, which does not involve molecular crowding. The findings of the new study and the lessons of evolution suggest that bioengineers will need to build crowding into artificial cells if synthetic genetic circuits are to function as they would in real cells.

The research team developed its artificial cellular system using molecular components from bacteriophage T7, a virus that infects bacteria that is often used as a model in synthetic biology.

To mimic the crowded intracellular environment, the researchers used various amounts of inert polymers to gauge the effects of different density levels.

Crowded but connected

Crowding in a cell isn’t so different from a crowd of people, Tan says. If only a few people are in a room, it’s easy for people to mingle or even to become isolated. But in a crowded room where it’s hard to move around, individuals often will tend to stay close to each other for extended periods. The same thing happens in a cell. If the intracellular space is crowded, binding between molecules increases.

Notably, the researchers found that the dense environments also made gene transcription less sensitive to environmental changes. When the researchers altered concentrations of magnesium, ammonium, and spermidine—chemicals that modulate the stability and binding of macromolecules—they found higher perturbations of gene expression in low-density environments than in high-density environments.

“Artificial cellular systems have tremendous potential for applications in drug delivery, bioremediation, and cellular computing,” Tan says.

“Our findings underscore how scientists could harness functioning mechanisms of natural cells to their advantage to control these synthetic cellular systems, as well as in hybrid systems that combine synthetic materials and natural cells.”

The National Institutes of Health and the National Science Foundation supported the research, as did Tan’s Lane Postdoctoral Fellowship and his Society in Science-Branco Weiss Fellowship. The Lane Center for Computational Biology is part of Carnegie Mellon’s School of Computer Science.

Source: Carnegie Mellon University

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