In a virtual cell, model proteins near the membrane tend to diffuse along the membrane. Also, motions near the membrane are more strongly correlated than motions in the cell’s interior. These observations suggest that molecular interactions near the membrane may be facilitated, and that there may be additional time for signal transduction. [Edmond Chow]
In a virtual cell, model proteins near the membrane tend to diffuse along the membrane. Also, motions near the membrane are more strongly correlated than motions in the cell’s interior. These observations suggest that molecular interactions near the membrane may be facilitated, and that there may be additional time for signal transduction. [Edmond Chow]

Every day inside a cell is like New Year’s Eve in Times Square. The cell is stuffed full of molecules that are, like New Year’s revelers, hemmed in on all sides. These molecules are usually assumed to jostle against each other and diffuse about as though they were unconfined. But do intracellular molecules really move this way? The question is like asking whether the party animals in Times Square behave the same way whether they are in the middle of the crowd or pressed against the police barricades.

Whether you’re studying how molecules move within the confines of the cell, or how people move in crowded spaces, computer simulations come in handy. In the case of intracellular molecules, computer simulations have demonstrated that the molecules tend to linger near cell walls. At the same time, confinement in the viscous liquid inside cells causes particles to move about more slowly than they would in unconfined spaces.

These findings emerged from an interdisciplinary collaboration between computational scientist Edmond Chow, Ph.D., and biologist Jeffrey Skolnick, Ph.D., at the Georgia Institute of Technology. According to these scientists, their findings may be particularly relevant to studies of molecular signaling.

Details of the scientists’ work appeared November 16 in the Proceedings of the National Academy of Sciences, in an article entitled, “Effects of confinement on models of intracellular macromolecular dynamics.” The article noted that confinement yields an overall slowdown in motion. Also, motion in the interior of the cell can be effectively modeled as if the cell were infinitely large. Most interesting, however, was the observed layering of particles at the cell wall due to steric interactions in the confined space.

“Motions of nearby particles are also strongly correlated at the cell wall, and these correlations increase when hydrodynamic interactions are modeled,” wrote the authors of the PNAS article. “Further, particles near the cell wall have a tendency to remain near the cell wall. A consequence of these effects is that the mean contact time between particles is longer at the cell wall than in the interior of the cell.”

Reflecting on the significance of these findings, the authors suggested that confinement not only affects the interactions between particles, it also points to a mechanism that could affect signal transduction and other processes near the membrane of biological cells.

“The lifetimes of these interactions get enhanced, and that is what's needed there for biological interactions to occur within the cell,” said Dr. Skolnick. “This lingering near the wall could be important for understanding other interactions because if there are signaling proteins arriving from other cells, they would associate with those particles first. This could have important consequences for how signals are transduced.”

“We are setting the stage for what we need to do to simulate a real cell,” asserted Dr. Skolnick. “We would like to put enough of a real cell together to be able to understand all of the cellular biochemical principles of life. That would allow us to ask questions that we can't ask now.”

Scientists, of course, can study real cells. But the simulation offers something the real thing can't do: The ability to turn certain forces on or off to isolate the effects of other processes. For instance, in the simulated cell Drs. Skolnick and Chow hope to build, they'll be able to turn on and off the hydrodynamic forces, allowing them to study the importance of these forces to the functioning of real cells. In general, results from simulations can suggest hypotheses to be confirmed or rejected by experiment.








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