Better sensing through empty receptors

New model suggests cells may be more sensitive to their environment than previously thought

Cells may benefit by paying attention to sensors that are still open for business. A new model finds that, contrary to conventional wisdom, sensors on the outside of a cell that have not yet detected a chemical signal may be more useful than those that have already detected the signal, a study set to appear in Physical Review Letters suggests. By reconsidering how a cell sorts information, Ned Wingreen of Princeton University and Robert Endres of Imperial College London found that these unbound sensors can collectively provide a clearer view of the environment. Single-celled organisms, such as bacteria and yeast, must accurately judge their landscape to find food and avoid trouble. Cells sense their surroundings through small proteins called receptors that coat the outer cell membrane. When a receptor grabs on to a particular molecule, like a sugar or an amino acid, the receptor can spur the cell to move toward or away from those molecules, a process called chemotaxis.  “Sensing can be life or death for cells, especially in the case of chemotaxis,” Wingreen says. “It’s a competitive world out there, so whoever senses it gets to eat it.” In 1977, Howard Berg and E.M. Purcell proposed a fundamental limit on how sensitive cells can be to a chemical’s concentration. This model assumed that cells sense the concentration of a chemical by detecting how long the chemical stays bound to a receptor. A cell would be more likely to move toward high concentrations of an attractant, such as a food signal, than low concentrations. But Wingreen and Endres wondered if cells, by focusing on a different piece of the incoming data, could be even better at detecting low concentrations than the Berg-Purcell limit predicted. “What is the best the cell can do?” Wingreen says. “What is the most information you can extract from the data?” Wingreen and Endres reasoned that perhaps cells use information about the rate at which unoccupied receptors bind with molecules. If this is true, how long a receptor holds onto that signal isn’t important information for the cell. A receptor that isn’t bound to anything still has potential to detect a chemical, but a receptor that’s already locked on to a chemical has no additional information to offer the cell. Wingreen and Endres calculated cells’ ability to detect molecules using data from only unoccupied receptors as they latched onto molecules. The researchers found that this method allowed cells to sense even lower concentrations of molecules. What’s more, the new method predicts that cells’ sensing abilities would be more accurate than previously thought. Berg, of Harvard University, says the new results are “interesting, but not profound. It’s a different way of thinking about the receptor binding problem” that offers a refinement on the previous notion, he says.     So far, the researchers don’t know if any cells actually implement this optimal strategy. “For me, the most interesting thing is looking at specific sensing systems,” Wingreen says. “Can we find an example where we think this is being used?” To get the benefits from this sensing system, cells would have to figure out a way to take already-bound receptors out of the equation. Biochemist Gerald Hazelbauer says that the proposed system may turn up in some cells.  “Experience shows that if one can think of a possible mechanism for a particular biological process, no matter how strange or unusual, there is probably a biological system or organism that utilizes that mechanism,” says Hazelbauer, of the University of Missouri in Columbia.

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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