ABOVE: Built with nature’s building blocks, the protein lawnmower helps researchers to better understand molecular motors. Designed by Erin Lemieux

The body operates as a well-oiled machine, relying on protein-based molecular motors to perform essential functions such as cell division, cargo transport, cell locomotion, and tissue maintenance. Inspired by nature’s motors, researchers have recreated artificial ones using DNA origami.1 However, Nancy Forde, a biophysicist at Simon Fraser University, sought to more closely recreate these biological machines with proteins, especially nonmotor proteins which seemed like a far off dream. “In nature, proteins do all the work, so we had this crazy idea of building synthetic protein motors,” said Forde. 

Headshot of Nancy Forde.
Nancy Forde aims to better understand the fundamental principles of molecular machines by creating them from scratch with nature’s building blocks. 
Simon Fraser University

In a recent paper published in Nature Communications, she and her colleagues from the University of New South Wales and Lund University unveiled their protein-based artificial motor, dubbed the Lawnmower, which is capable of motion comparable to biological motors.2 While existing protein motors have been based on naturally occurring motors, this proof-of-principle, synthetic platform demonstrates how nonmotor proteins can build motors. These results could help researchers better understand the intricate motor systems to advance nanotechnology applications.

Chapin Korosec, then a physics graduate student in Forde’s group and now a postdoctoral fellow in applied mathematics at York University, led this work. He constructed the Lawnmower, where the mower consisted of a central microspherical bead equipped with “blades”: thousands of nanoscale trypsin proteases along the surface.3 Then the researchers created a “lawn” laden with millions of short protein fragments bound to a silica surface for the Lawnmower to traverse.

For movement, the Lawnmower propelled itself using the burnt-bridge ratchet (BBR) principle. This molecular motion harnesses biological reactions where the trypsin blades bound and cleaved the peptide grass, directing the Lawnmower to preferentially seek out the next patch of energy rich uncut peptide grass. 

First, Korosec test drove the Lawnmowers by placing them onto a two-dimensional (2D) peptide lawn to roam around freely. One lawn was lush with peptides, while the other was bare. Using a microscope, he tracked the motor’s movements for 12 hours, and the differences were striking. In a field brimming with peptides, the Lawnmowers exhibited movement consistent with the BBR mechanism and outpaced their counterparts on bare, peptide-free lawns by traveling much further and faster. “We found that the protein Lawnmower could stall. It doesn’t always continuously move. Instead, it moves in bursts. It sits, jiggles, then bursts forward again,” said Korosec. 

Headshot of Chapin Korosec.
Inspired by nature’s molecular motors, Chapin Korosec simulated, designed, and implemented artificial motors in the laboratory.
Chapin Korosec

Since the Lawnmower demonstrated directional movement, the researchers wanted to see if it also exhibited track-guided motility, a feature ubiquitous to biological molecular motors.4 The team designed narrow tracks with either lush peptide lawns or bare lawns along the bottom of the channels. Lawnmowers displayed motion like the behavior observed on the 2D lawn, rolling along the predefined track.

The Lawnmower demonstrated autonomous motility and provided a platform for future protein-based motors. “These [motors] have the potential to do some good work,” remarked Henry Hess, a biomedical engineer at Columbia University who was not involved in the study. “This study really pushes the proteins to the forefront. My hope is that the proteins assert themselves … towards understanding complex nanoscale functions... in terms of what path they're taking and then how you can interrupt the motion and pick it back up.” 

Harnessing proteins to develop artificial protein motors is an ongoing challenge. However, the Lawnmower demonstrates the possibility of building motors from nonmotor protein parts. Next, the researchers hope to explore various properties such as power, speed, and directionality. “In designing protein-based motors beyond the Lawnmower, we are learning whether and how it is possible to treat proteins as modular, as components in a toolkit,” remarked Forde. “In such cases, it will be easier to build motors out of different parts and compare their designed function with our predictions.” This nanotechnology opens avenues in constructing future artificial protein motors with potential applications to a range of problems. 

References

  1. Bazrafshan, A. et al. Tunable DNA origami motors translocate ballistically over μm distances at nm/s speeds. Angew. Chem. Int. Ed. 2020;59(24):9514-9521
  2. Korosec CS, et al. Motility of an autonomous protein-based artificial motor that operates via a burnt-bridge principle. Nat Commun. 2024;15:1511.
  3. Kovacic S, et al. Design and construction of the lawnmower, an artificial burnt-bridges motor. IEEE Trans. NanoBiosci. 2015;14(3):305-312.
  4. Schliwa M, Woehlke G. Molecular motors. Nature. 2003;422(6933):759-765.