Using large-scale computer modeling, researchers have shown the effects of confinement on macromolecules inside cells — and taken the first steps toward simulating a living cell, a capability that could allow them to pose “what-if” questions impossible to ask in real cells.
The work could help scientists better understand signaling between cells and provide insights for designing new classes of therapeutics. For instance, the simulations showed that particles within crowded cells tend to linger near cell walls, while confinement in the viscous liquid inside cells causes particles to move about more slowly than they would in unconfined spaces.
The research is a collaboration between Edmond Chow, an associate professor in Georgia Tech’s School of Computational Science and Engineering, and Jeffrey Skolnick, a professor in Georgia Tech’s School of Biology. Their goal is to develop and study models for simulating the motions of molecules inside a cell, and also to develop advanced algorithms and computational techniques for performing large-scale simulations.
Skolnick compared the interior of a living cell to a large New Year’s Eve party. “It’s kind of like a crowded party that has big people and little people, snakes — DNA strands — running around, some really large molecules, and some very small molecules,” he said. “It’s a very heterogeneous and dense environment with as much as 40 percent of the volume occupied.”
While the simulations didn’t include the DNA strands or metabolite particles also found in cells, they did include up to a half-million objects. Using physics principles, Skolnick and Chow considered what the particles would do in a cell just a few microns in diameter.
“From the results of the computer simulations, we can measure things that we think might be interesting, such as the diffusion rates near the walls and away from the walls,” Chow said.
Supported by the National Science Foundation, the results were reported in the journal Proceedings of the National Academy of Sciences.
— John Toon