Comparing notes boosts cells sensing accuracy
To decide whether and where to move in the body, cells must read chemical signals in their environment. Individual cells do not act alone during this process, two new studies on mouse mammary tissue show. Instead, the cells make decisions collectively after exchanging information about the chemical messages they are receiving.
Every cell in a body has the same genome but they can do different things and go in different directions because they measure different chemical signals in their environment. Those chemical signals are made up of molecules that randomly move around.
“Cells can sense not just the precise concentration of a chemical signal, but concentration differences,” Nemenman says. “That’s very important because in order to know which direction to move, a cell has to know in which direction the concentration of the chemical signal is higher. Cells sense this gradient and it gives them a reference for the direction in which to move and grow.”
Berg and Purcell understood the best possible margin of error — the detection limit — for such gradient sensing. During the subsequent 30 years, researchers have established that many different cells, in many different organisms, work at this detection limit. Living cells can sense chemicals better than any humanmade device.
It was not known, however, that cells can sense signals and make movement decisions collectively.
“Previous research has typically focused on cultured cells,” Nemenman says. “And when you culture cells, the first thing to go away is cell-to-cell interaction. The cells are no longer a functioning tissue, but a culture of individual cells, so it’s difficult to study many collective effects.” More.
(Does anyone else get the feeling I do that people other than us are spooked by all this and beginning to have second thoughts about Darwinism?
Here’s my question: What do you end up having to believe, compared to what you would have had to believe fifty years ago, in order to accept the stuff they huff over at, say, Panda’s Thumb?)
See also: What can we hope to learn about animal minds? (including life forms we don’t think have minds, in the usual sense, and yet … )
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Here’s the abstract (1 of 2):
Collective cell responses to exogenous cues depend on cell–cell interactions. In principle, these can result in enhanced sensitivity to weak and noisy stimuli. However, this has not yet been shown experimentally, and little is known about how multicellular signal processing modulates single-cell sensitivity to extracellular signaling inputs, including those guiding complex changes in the tissue form and function. Here we explored whether cell–cell communication can enhance the ability of cell ensembles to sense and respond to weak gradients of chemotactic cues. Using a combination of experiments with mammary epithelial cells and mathematical modeling, we find that multicellular sensing enables detection of and response to shallow epidermal growth factor (EGF) gradients that are undetectable by single cells. However, the advantage of this type of gradient sensing is limited by the noisiness of the signaling relay, necessary to integrate spatially distributed ligand concentration information. We calculate the fundamental sensory limits imposed by this communication noise and combine them with the experimental data to estimate the effective size of multicellular sensory groups involved in gradient sensing. Functional experiments strongly implicated intercellular communication through gap junctions and calcium release from intracellular stores as mediators of collective gradient sensing. The resulting integrative analysis provides a framework for understanding the advantages and limitations of sensory information processing by relays of chemically coupled cells. (paywall) – David Ellison, Andrew Mugler, Matthew D. Brennan, Sung Hoon Lee, Robert J. Huebner, Eliah R. Shamir, Laura A. Woo, Joseph Kim, Patrick Amar, Ilya Nemenman, Andrew J. Ewald, and Andre Levchenko. Cell–cell communication enhances the capacity of cell ensembles to sense shallow gradients during morphogenesis. PNAS, January 2016 DOI: 10.1073/pnas.1516503113
Here’s the significance statement (of 2 of 2):
Knowing which way to move is crucial for many biological processes, from organismal development to migration of cancer cells and from motion of microbes to wound healing. To find their preferred directions, biological systems compare concentrations of a chemical cue at their different edges. The comparison requires information from these different locations to be communicated to the same place. However, all communication is noisy (just think of the childhood game “telephone”). This communication noise, as well as noise in the individual measurements themselves, sets the accuracy of the direction sensing. Here we quantify the importance of the communication noise and propose a mechanism that can improve the accuracy of direction sensing. (paywall) – Andrew Mugler, Andre Levchenko, and Ilya Nemenman. Limits to the precision of gradient sensing with spatial communication and temporal integration. PNAS, January 2016 DOI: 10.1073/pnas.1509597112