Bacteria may be simple, single-celled organisms, but they still have a surprisingly sophisticated way of sensing and responding to their environment. Tom Shimizu, group leader at AMOLF and senior author of the study, explains that bacteria use networks of thousands of proteins to judge whether conditions are improving or worsening.
Witnessing protein activity within live cells
Inspired by the fascinating role proteins play, the researchers developed a method to measure this protein activity within individual living cells. “It’s quite analogous to human brain waves,” explains Tom. “The level of activity inside the cell is always fluctuating, even in ‘quiet’ environments without any sensory cues.”
Co-first author Johannes Keegstra (currently ETH Zurich) realized that the protein switching he witnessed was not entirely random but could be studied as a signal. He came to this conclusion after carefully scrutinizing the fluctuating signals in thousands of individual cells. He noticed a particularly intriguing pattern in a subset of the cells. “It was as if the bacteria were having some sort of epileptic seizure. All of the sensory proteins in the cell were randomly switching between no activity and full activity, and strikingly, they did so all at the same time.”
Life on the brink: balancing order and disorder
Precisely measuring the timing of these synchronized switching events led to the breakthrough reported in the study. Comparing the timings of thousands of switches to a mathematical model of the molecular network, the team found a surprising explanation. The strength of interactions between neighboring proteins – a parameter known as the coupling energy – is set very close to a value right on the boundary between order and disorder.
Theory has long suggested that many biological systems work best when they operate near a ‘critical point’. This is a balanced state where the system is neither too rigid nor too chaotic. At this point, the system can respond sensitively to changes in its environment, without getting locked in extreme or unresponsive states.
Like applause in a concert hall
To understand the idea of a critical point, imagine an audience after a concert. Each person is unsure whether to applaud and looks to their neighbors for cues. If everyone strongly follows their neighbors, the audience ends up either all applauding or staying silent, with no one willing to act differently. If people barely pay attention to others, applause becomes random and uncoordinated. Theory predicts a special balance between these extremes, the critical point, where the audience can easily switch between applause and silence. Interestingly, protein molecules in bacteria appear to behave in a similar way.
Bacterial sweet spot
On the one hand, bacteria benefit from strong coupling because it increases their sensitivity to signals. On the other hand, it also slows down their response time. Co-first author Fotios Avgidis (currently at Yale) says: “By staying poised near the transition between order and disorder, the cell achieves the best of both worlds: strong signal amplification without drastically diminishing response speed. Such a balance is likely beneficial in natural environments where bacteria have to respond rapidly to short-lived cues.”
Information in Matter
The new findings suggest that bacteria are able to control how they set their ‘brains’, and this intriguing capability is what AMOLF’s Physics of Behavior group continues to study. Tom Shimizu: “There are many open questions about how bacteria achieve this special tuning, and how that affects information they collect from their environment. Answering those questions will bear lessons also about the design of many other biological systems, as well as future artificial sensory systems in synthetic biology and in robotics. We’re excited to work closely with other groups in the Information in Matter theme at AMOLF to make progress on these big questions.”
Learn more
If you have questions about this research, please contact Tom Shimizu.
This paper was published in Nature Physics: Spontaneous switching in a protein signalling array reveals near-critical cooperativity
