Scientists have unveiled a groundbreaking explanation for how swimming bacteria alter their direction, shedding new light on a molecular machine that has captivated biologists for decades. This discovery, detailed in a recent Nature Physics publication, challenges long-held beliefs about bacterial movement and offers fresh insights into the intricate workings of flagella, the propeller-like tails that enable bacteria to navigate through liquids.
Bacteria propel themselves by rotating their flagella, which can spin either clockwise or counterclockwise. For years, this directional switching was attributed to a ‘domino effect’ model, where proteins along the flagellum’s length exerted pressure on each other to trigger a change in rotation. However, new research from the Flatiron Institute’s Henry Mattingly and Yuhai Tu proposes a different mechanism. Their findings suggest that an active tug-of-war among distant proteins, rather than passive pressure, drives the switch.
The Problem With the Domino Effect
The flagellar motor, a marvel of molecular machinery, has been a subject of intense study. Composed of 34 proteins arranged in a central ring, it is powered by stators—structures that channel electrically charged atoms to drive rotation. The ring proteins’ rotation direction is influenced by the binding of a molecule called CheY-P, which alters protein conformation and promotes spinning in a specific direction.
“CheY-P concentration depends on what the cell is experiencing outside, in its environment,” explains Mattingly, an associate research scientist at the Center for Computational Biology. “It’s like a relay from what the cell senses to how it responds with changes in behavior.”
In the traditional equilibrium model, scientists posited that neighboring proteins would eventually align through a domino effect. However, when researchers examined the frequency of directional switches, the data did not align with this model. Instead of a memoryless statistical pattern, the distribution showed a peak in the time spent rotating in one direction, indicating a non-equilibrium process.
“If you see this pattern, then the effect cannot be a purely equilibrium phenomenon,” says Tu. “There had to be something else going on.”
A Tug-of-War Inside the Tail
Mattingly and Tu’s research suggests that motor switching is not a passive process but involves energy injection into the system. Recent discoveries about the motor’s structure informed their theory. The C-ring acts as a central gear with each protein as a tooth, while stators function as smaller gears. The interaction between these gears determines the motor’s direction.
Conflicts arise when different teeth adopt different conformations, leading to a tug-of-war. “Imagine all the teeth are in the same outer conformation. Then one of them flips,” Mattingly describes. “As the gear turns, that lone dissenter eventually contacts a stator that pushes it in the opposite direction. It’s like a mechanical tug-of-war.”
This process, termed “global mechanical coupling,” highlights that the forces driving each tooth are not solely determined by neighboring interactions but involve a collective process across the motor. This mechanism explains the observed peak in directional switching, as stators actively inject energy and drive the system out of equilibrium.
“Global mechanical coupling explains what the earlier, purely equilibrium theory couldn’t, that switching is energy-driven, directional, and cooperative,” says Tu.
Unraveling Mysteries in the Flagella and Beyond
With this new model, researchers aim to enhance our understanding of other nonequilibrium systems in biology. “Our results make sense to me because I believe living systems always operate out of equilibrium,” Tu notes. “They dissipate energy, and that energy is essential for biological function.”
The team plans to refine their model with additional experimental data, as it predicts a peak in counterclockwise durations on a shorter timescale than observed. Understanding flagella could also inform studies of more complex biological systems.
“It’s so well studied that it becomes a perfect system to test ideas—and what we learn here often helps us think about more complex biology,” Mattingly adds.
Tu emphasizes the broader implications for bacterial chemotaxis research. “Every so often people say, ‘This is a dead field.’ Every time that turns out to be wrong. There’s always another layer.”
