Ultrasensitivity without conformational spread: A mechanical origin for non-equilibrium cooperativity in the bacterial flagellar motor

TL;DR

This paper proposes a novel mechanical mechanism for ultrasensitivity in bacterial flagellar motors, demonstrating that non-equilibrium cooperativity can arise from global mechanical coupling without conformational spread.

Contribution

It introduces the concept of global mechanical coupling driven by mechanical torques as a new mechanism for ultrasensitivity in bacterial flagellar motors, challenging previous conformational spread models.

Findings

Motor cooperativity increases with the number of stators.

Re-analysis of existing data supports the model's predictions.

Out-of-equilibrium operation enhances response speed and cooperativity.

Abstract

Flagellar motors enable bacteria to navigate their environments by switching rotation direction in response to external cues with high sensitivity. Previous work suggested that ultrasensitivity of the flagellar motor originates from conformational spread, in which subunits of the switching complex are strongly coupled to their neighbors as in an equilibrium Ising model. However, dynamic single-motor measurements indicated that rotation switching is driven out of equilibrium, and the mechanism for this dissipative driving remains unknown. Here, based on recent cryo-EM structures, we propose that local mechanical torques on motor subunits can affect their conformation dynamics. This gives rise to a tug of war between stator-associated subunits, which produces cooperative, non-equilibrium switching responses without requiring nearest-neighbor interactions. Since subunits are effectively coupled at a distance, we call this mechanism ``Global Mechanical Coupling." Our model makes a qualitatively new prediction that the motor response cooperativity grows with the number of stators driving rotation. Re-analyzing published motor dose-response curves in varying load conditions, we find tentative experimental evidence for this prediction. Finally, we show that operating out of equilibrium enables motors to achieve high cooperativity with faster responses compared to equilibrium motors. Our results suggest a general role for mechanics in sensitive chemical regulation.