Why many cells are better than one

Oct 12, 2011

Researchers from Johns Hopkins have quantified the number of possible decisions that an individual cell can make after receiving a cue from its environment, and surprisingly, it's only two.

The first-of-its-kind study combines live-cell experiments and math to convert the inner workings of the cell decision-making process into a universal mathematical language, allowing in cells to be compared with the of machines.

The research published on September 15 in Science also demonstrates why it's advantageous for cells to cooperate to overcome their meager individual decision-making abilities by forming .

"Each cell interprets a signal from the environment in a different way, but if many cells join together, forming a common response, the result can eliminate the differences in the signal interpretation while emphasizing the common response features," says Andre Levchenko, Ph.D., associate professor of and member of the Institute for . "If a single blood vessel cell gets a signal to contract, it is meaningless since all the surrounding cells in the blood vessel need to get the message to narrow the blood vessel. Cell collaboration does wonders in terms of their ability to transfer information and convert it into decision-making."

One bit of information represents two choices: yes or no, on or off, or one or zero in binary code, used by computer programmers. Two bits doubles the amount of choices to four and so on for each bit added.

To determine how many bits of information a cell has for each decision, the researchers had to measure a real biological decision in progress. They decided to look at a well-known cell , a protein called (TNF), responsible for turning on the inflammation response in the body. When cells detect TNF on their surface, they transmit a message that sends a messenger protein into the nucleus to turn on inflammation genes.

The researchers administered different amounts of TNF to mouse cells in dishes, and then they determined whether the messenger went to the nucleus. They bound the messenger with a glowing tag; the more messenger present in the nucleus, the brighter the nucleus would appear under a microscope. The researchers used a computer program to quantify the brightness of the nucleus after the addition of TNF. From this, they calculated a single cell's response to be 0.92 bits of information, allowing for two possible decisions.

"What we get from this information is that the cell can only reliably detect the presence of the signal or not, nothing more precise," says Levchenko. "This was a little bit dissatisfying because we were hoping that the cells could recognize many more levels of the input and use that to make more decisions than just two."

The researchers tested other scenarios to see if cells could respond in more ways. They looked at decision outputs other than , like development and cell survival. They also looked to see if the cell's response to a certain stimulus changed over time, as well as explored whether receiving different input signals that led to the same outcome could boost decision-making potential. None of these different situations drove cells to show greater decision-making ability. Cells seem to have distinct limits to the amount of information they intake that confines the number of decisions they can make, says Levchenko.

Finally, the researchers investigated the idea that cells could collectively respond to input to make decisions together. They went back to quantifying the brightness of the nucleus in response to TNF, but this time they examined clusters of cells and compiled this data into their equation. They found that clusters of as few as 14 cells could produce 1.8 bits of information, corresponding to somewhere from 3 to 4 different potential decisions for the cluster.

The fact that combinations of cells can make more decisions suggests why being multicellular is such a good thing in the animal world and why cells can sometimes achieve so much more if they are working together than separately, says Levchenko.

"We've learned that there is a clear limit on what can happen in a cell, and we are actually quantifying for the first time what the cells can and can't do," says Levchenko. "A lot of people were surprised that this was even possible. This framework we've laid will allow us to test what kind of tricks use, other than being multicellular, to expand their decision repertoire."

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Provided by Johns Hopkins Medical Institutions

4.5 /5 (2 votes)

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User comments : 7

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Nanobanano
5 / 5 (1) Oct 12, 2011
None of these different situations drove cells to show greater decision-making ability. Cells seem to have distinct limits to the amount of information they intake that confines the number of decisions they can make.


Not looking at this properly.

Cells have more than one carrier or receptor.

Any one chemical is a "bit" signal. Your decision following a single binary digit input is typically going to be just an "either/or" response. However, you can have more than one type of stimulus to a cell.

You'd never expect a simple "on/off" input to produce more than two outputs, unless one or more outputs are randomly determined.

"if/then/else"

If (1)
then
special stuff
else
do normal functions(i.e. typically nothing)
hush1
5 / 5 (1) Oct 12, 2011
All cells come with threshold. The incoming signal is energy. This energy is distributed. This distribution "decides" if a cell's threshold criteria is met.

The author's anthropomorphising is more than a disservice.
Obfuscating simple biophysical states with "decision making" and "interpretation skills" makes no sense.
pauljpease
4 / 5 (1) Oct 12, 2011
None of these different situations drove cells to show greater decision-making ability. Cells seem to have distinct limits to the amount of information they intake that confines the number of decisions they can make.


Not looking at this properly.

Cells have more than one carrier or receptor.

Any one chemical is a "bit" signal. Your decision following a single binary digit input is typically going to be just an "either/or" response. However, you can have more than one type of stimulus to a cell.

You'd never expect a simple "on/off" input to produce more than two outputs, unless one or more outputs are randomly determined.

"if/then/else"

If (1)
then
special stuff
else
do normal functions(i.e. typically nothing)

But it's NOT a simple "on/off" input. Did the cell bind to 10 TNF molecules, or 100? What they're saying is that the cell responds one way above a threshold, and responds a different way below the threshold, but with groups there can be more responses.
hush1
5 / 5 (1) Oct 12, 2011
Please examine the TNF pathway.

http://www.genego..._420.php

Up until now I have simplified all my commentary - to reach as many readers as possible.

Note of interest: All cells 'fire' continuously. A cell's threshold that is exceeded changes the 'fire' rate of a cell. Additionally, a cell's threshold changes with the number of times the cell's threshold is exceeded.

A cell's specificity determines the scope a cell's response - Cell specificity determines what signals to a cell's predetermined numbered responses and threshold receptivity (gene expression - here as the protein TNF) are accessible.

You can simplify as I have in my description in the first comment. The author misleads with an incorrect explanation of a mechanism the author describes correctly.
hush1
not rated yet Oct 12, 2011
Why 4 rating? I actually believe any response a cell's is capable of depends on - in part at least - what type of cell.
hush1
not rated yet Oct 12, 2011
The correct wording:
Researchers from Johns Hopkins have quantified the number of possible responses that an individual cell can make after receiving a cue from its environment, and surprisingly, it's unlimited.

Much better. And correct. :) Send check please.

So how can a limited numbers of responses constricted by cell's function still be unlimited?

A cell sends and receives simultaneously. Limited responses can be repeated endlessly and the timing of endlessly repeated responses has a duration that makes the cell's sent response unique:

Different timing of the same signal 'means' 'new' 'things' for neighboring cells receiving the 'same' signal.

A cell sending the same response (signal) that continually weakens with time is additionally new information updates for neighboring cells:

Different strengths of the same signal 'means' 'new' 'things' for neighboring cells receiving the 'same' signal.
antialias_physorg
5 / 5 (1) Oct 13, 2011
Not looking at this properly.

Cells have more than one carrier or receptor.

The article was about the principle of reaction of one cell to one stimulus with varying degrees of intensity - not the number of reactions possible by a cell to different stimuli ior over a the entire history of the cell.
Within the context of TNF the response seems to be limited to on/off (1 bit).

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