Biochemical cell signals quantified for first time

Just as cell phones and computers transmit data through electronic networks, the cells of your body send and receive chemical messages through molecular pathways. The term “cell signaling” was coined more than 30 years ago to describe this process.

Now, for the first time, scientists have quantified the data capacity of a biochemical signaling pathway and found a surprise – it’s way lower than even an old-fashioned, dial-up modem.

“This key biochemical pathway is involved in complex functions but can transmit less than one bit – the smallest unit of information in computing,” says Ilya Nemenman, an associate professor of physics and biology at Emory University. “It’s a simple result, but it changes our view of how cells access chemical data.”

The journal Science is publishing the discovery by Nemenman and colleagues from Johns Hopkins University, including Andre Levchenko, Raymond Cheong, Alex Rhee and Chiaochun Joanne Wang.

During the 1980s, cell biologists began identifying key signaling pathways such as nuclear factor kappa B (NF-kB), known to control the expression of genes in response to everything from invading pathogens to cancer. But the amount of information carried by chemical messengers along these pathways has remained a mystery.

“Without quantifying the signal, using math and computer analysis to attach a number to how much information is getting transmitted, you have a drastically incomplete picture of what’s going on,” says Nemenman, a theoretical biophysicist. “It was a shock to learn that the amount of information getting sent through this pathway is less than one bit, or binary digit.”.“That’s only enough information to make one binary decision, a simple yes or no.”

And yet NF-kB is regulating all kinds of complex decisions made by cells, in response to stimuli ranging from stress, free radicals, bacterial and viral pathogens and more. “Our result showed that it would be impossible for cells to make these decisions based just on that pathway because they are not getting enough information,” Nemenman says. “It would be like trying to send a movie that requires one megabit per second through an old-style modem that only transmits 28 kilobits per second.”

They analyzed the signals of several other biochemical pathways besides NF-kB and got a similar result, suggesting that a data capacity of less than one bit could be common. So if cells are not getting all the information through signaling pathways, where is it coming from?

“We’re proposing that cells somehow talk with each other outside of these known pathways,” Nemenman says. “A single cell doesn’t have enough information to consider all the variables and decide whether to repair some tissue. But when groups of cells talk to each other, and each one adds just a bit of knowledge, they can make a collective decision about what actions to take.”