How a Molecular Motor Minimizes Energy Waste
Within every biological cell is an enzyme, called adenosine triphosphate (ATP) synthase, that churns out energy-rich molecules for fueling the cell’s activity. New experiments investigate the functioning of this “energy factory” by artificially cranking one of the enzyme’s molecular motors [1]. The results suggest that maintaining a fixed rotation rate minimizes energy waste caused by microscopic fluctuations. Future work could confirm the role of efficiency in the evolutionary design of biological motors.
ATP synthase consists of two rotating molecular motors, Fo and F1, that are oriented along a common rotation axis and locked together so that the rotation of Fo exerts a torque on the shaft in the middle of F1. The resulting motion within F1 helps bring together the chemical ingredients of the molecule ATP, which stores energy that can later be used in cellular processes.
Researchers have determined the motors’ atomic structures, but the details of the coupling between Fo and F1 are unclear. Fo is embedded in a membrane. Protons flow across this membrane and drive Fo’s rotation, but directly measuring Fo’s torque is challenging because it would require reproducing the membrane and its chemical environment in a controllable laboratory setting, says Shoichi Toyabe of Tohoku University in Japan.
Toyabe and his colleagues devised an approach for overcoming this challenge. They reasoned that Fo could exert torque on F1 in different ways, but evolution would favor a more energetically efficient driving mechanism. To explore the role of efficiency, the team replaced Fo with an artificial motor and used it to drive F1’s rotation in one of two ways: either by applying constant torque or by fixing the rotation rate with a variable torque. Artificially rotating the F1 motor is not new, but no one has previously been able to drive the motor in two distinct modes and measure their efficiencies.
The researchers started by isolating the F1 motor from Bacillus bacteria. They fixed the motor’s outer frame to a glass slide and attached a pair of polystyrene beads to the F1 shaft, using a kind of chemical glue. The researchers then brought in a set of electrodes and applied a time-varying voltage, which caused the beads to turn the shaft around its axis, just as Fo would do. The system was bathed in a solution containing the ATP ingredients so that the F1 motor performed the same chemical assembly that it does in a cell.
To find the efficiency in each mode, the team divided the output energy—determined from the F1 shaft’s total rotation—by the input energy supplied by the electrodes. The results showed that the constant-turning mode was more efficient than the constant-torque mode.
To explain these observations, team member David Sivak and his colleagues at Simon Fraser University in Canada modeled the effects of fluctuations on the experimental system. These fluctuations come from random thermal motions of the atoms, and they can, for example, nudge the rotation along, or they can push against it. “Some fluctuations hurt and some fluctuations help, but the resisting ones hurt more than the assisting ones help,” Sivak says. He explains that the constant-turning mode better balances the positive and negative effects and is thus more efficient than the constant-torque mode.
The researchers argue that their work implies a general guiding principle for molecular machines: Running at a constant speed can suppress the effect of random fluctuations and minimize energy waste. Toyabe says that a similar principle applies to macroscopic motors: “It is often said that driving at a steady speed is the most efficient way to drive a car, as sudden breaking or acceleration typically costs additional energy.”
Although a constant-turning mode has advantages, it’s not clear that Fo adopts this strategy. The motor has complicated interactions with its cellular environment that might favor a more complex driving mode. The researchers say that future experiments may uncover new clues about this mechanical behavior by combining Fo with F1 in a controlled, laboratory setting.
“The team’s approach to isolate and manipulate the mechanical motion of F1 is elegant, clever, and highly efficient,” says biophysicist Édgar Roldán from the International Centre for Theoretical Physics in Italy. He notes that the researchers performed a control experiment, in which the artificial motor turned freely without attachment to F1. In this case, with “biology” removed, the mechanical system showed no difference in efficiency between the two driving modes. Thus, a sensitivity to driving modes may be an important footprint of biological activity, Roldán says.
–Michael Schirber
Michael Schirber is a Corresponding Editor for Physics Magazine based in Lyon, France.
References
- T. Mishima et al., “Efficiently driving F1 molecular motor in experiment by suppressing nonequilibrium variation,” Phys. Rev. Lett. 135, 148402 (2025).