Scientists have uncovered a groundbreaking explanation for how swimming bacteria change direction, offering fresh insights into one of biology’s most intensively studied molecular machines. This discovery, published in Nature Physics, challenges the longstanding equilibrium ‘domino effect’ model and proposes an active ‘tug-of-war’ mechanism instead.
Bacteria navigate through liquids using propeller-like tails called flagella, which alternate between clockwise and counterclockwise rotation. For decades, this switching behavior was attributed to a passive model where proteins lining the bacterium’s tail exert pressure on their neighbors, prompting a change in rotational direction. However, new research from the Flatiron Institute’s Henry Mattingly and Yuhai Tu suggests a different mechanism, informed by experimental measurements of the flagellar motor’s molecular structure.
The Problem With the Domino Effect
The flagellar motor, a long-studied structure, is composed of 34 proteins arranged in a large central ring, powered by smaller structures called stators. These stators allow electrically charged atoms to flow in and drive the rotation. The ring proteins control the direction of rotation based on signals from a molecule called CheY-P. When CheY-P binds to a protein, it influences the protein’s conformation, promoting spinning in one direction or the other.
In the original equilibrium model, scientists proposed that disagreement among neighboring proteins would be resolved through a domino effect. However, experimental data revealed inconsistencies with this model. The observed distribution of time spent rotating in one direction showed a peak, which is not possible in an equilibrium system.
“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 reasoned that switching the motor’s rotational direction must involve energy injection, influencing how and when the motor switches. Recent discoveries about the motor’s physical structure informed their theory. The C-ring acts as a central gear, with each protein as a tooth. Stators, functioning as smaller gears, always rotate clockwise and make contact with the teeth of the large gear.
Conflicts arise when different teeth adopt different conformations, leading to a mechanical tug-of-war. If enough teeth dissent, the entire motor changes direction. This process, termed “global mechanical coupling,” highlights that forces driving each tooth are determined by interactions across the motor, not just by neighboring teeth.
“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, the team aims to enhance understanding of nonequilibrium systems in living organisms. “Our results make sense to me because I believe living systems always operate out of equilibrium,” says Tu. “They dissipate energy, and that energy is essential for biological function. This is a beautiful example of that principle.”
The researchers plan to refine their model with more experimental data, which could also influence understanding of more complex 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,” says Mattingly.
Tu adds that this research is significant for the field of bacterial chemotaxis, which continues to reveal new layers despite being considered a “dead field” at times. “Every so often people say, ‘This is a dead field.’ Every time that turns out to be wrong. There’s always another layer.”
