Scientists build first artificial protein motor that walks on DNA

Researchers have built an artificial protein motor that walks in a set direction along a strand of DNA. It moves one step at a time, under second-by-second control.

The motor is assembled from protein pieces that, on their own, cannot move at all.

Building a protein that walks has been a long-standing goal in synthetic biology, and until now no one had managed it from the ground up.

The work shrinks a functioning synthetic motor down to a single engineered protein. It gives scientists a controllable model for how the body’s own motors move.

A walker from scratch

The motor is named Tumbleweed, and the concept is not new. A group first proposed it on paper back in 2009.

Turning that sketch into a machine that actually works took another decade and a half.

Heiner Linke, a professor of nanophysics at Lund University, led the study in collaboration with the University of New South Wales (UNSW).

The researchers assembled the walker from parts that nature never built for movement.

Great possibilities with proteins

Each of the three feet is a bacterial protein that grips a specific DNA sequence. The grip is conditional. A foot only clamps down when its matching chemical signal is present in the surrounding fluid.

One foot answers to the amino acid tryptophan, another to cobalt ions, the third to a small molecule that cells use in metabolism.

None of these proteins evolved to move anything. On their own, they only grip and release.

Chained together in the right order and fed their signals on a schedule, they do something none of them can manage alone, which is to walk in a chosen direction.

The appeal of proteins, and the difficulty, come from the same source.

“Proteins are far more complex than other molecular building blocks and therefore offer much greater possibilities. But that same complexity also makes them more challenging to work with,” said Linke.

How the motor steps

The DNA track carries the three feet’s binding sites in a fixed, repeating order. The spacing is deliberate. Two neighboring feet can grip at once, but a foot cannot stretch past its neighbor to reach a more distant site.

Walking comes from changing the chemistry around the motor in a steady rhythm.

The team bathed Tumbleweed in pairs of chemical signals and switched those pairs in a repeating cycle, so its feet took hold and released one after another.

As one foot let go, the next was already reaching farther along, so at least one foot stayed attached the whole time.

That hand-over-hand pattern kept the motor on its track while it moved.

Chemistry keeps the motor moving

That cycling makes Tumbleweed a Brownian ratchet, a device that channels the random jostling of molecules into motion in one direction.

A foot binds when its signal is plentiful. When the team washes that signal away, the foot lets go, and each grip-and-release draws energy from the difference.

This is the same trick that runs the rotary motors inside living cells, among them the one that builds the cell’s chemical fuel.

Each of Tumbleweed’s steps covers about 16 nanometers, far too small to see directly.

An automated device flushed fresh solutions past the motor every seven seconds. That was quick enough to set the pace.

Yet slow enough to let even the slowest foot release before the next move. Reversing the order of the signals sends the motor walking the other way.

Watching it walk

Following a single protein as it takes 16-nanometer steps is not straightforward. The team tagged both the walker and its track with fluorescent dyes.

The dyes were chosen so the color of light they gave off changed depending on where the motor stood.

As the signals cycled, the dyes switched color in step with the swaps, molecule after molecule.

In one field of view the researchers followed more than 300 motors at once, and nearly all changed color in time with the solution changes.

When the motor missteps

Individual walkers managed as many as 11 steps before releasing the track for good. The stepping was not flawless, though.

About a third of the time, the gripping foot skipped its intended landing spot and reached for a farther one instead.

The researchers put that slip down to flexibility in both the DNA and the walker’s own legs. Even with the stumbles, the motor held its overall direction.

Missteps changed how far any single walker traveled, but they did not push it backward.

Biological motors behave much the same way. Molecular motors such as myosin, kinesin and dynein all take occasional wrong steps.

That stumbling is now regarded as a basic feature of how they work, not a flaw in this design.

Building the next generation

Earlier protein motors leaned on nature’s own machinery.

One earlier effort reworked dynein, a natural motor, so it could run along tubes built from DNA, keeping the biological motor’s moving parts intact.

Tumbleweed takes a different route. It carries no natural motor part and exists as a single engineered protein rather than a bulky assembly.

The team says this echoes how evolution builds new proteins, mixing and reusing existing pieces until a fresh ability appears.

Rethinking molecular motors

Other designs run without any outside help. A 2024 walker nicknamed the Lawnmower moves on its own, yet one study built it from a crowd of many proteins.

Tumbleweed makes the opposite trade, packing everything into one small protein that, for now, still needs a machine to feed it signals in order.

Designing proteins from scratch has advanced fast, and the work earned a share of the 2024 Nobel Prize in Chemistry.

Most designed proteins, though, settle into a single fixed structure. A motor has to move, and coaxing a designed protein into reliable, controllable motion has been the far harder task.

Next steps for Tumbleweed

For now, Tumbleweed depends on that outside clock, and the next goal is a walker that runs on chemical fuel by itself. Linke measures the distance still ahead in plain human terms.

“Right now, we have a one-year-old who can take a few steps while holding someone’s hand,” said Linke.

What was missing until now was proof that a protein could be built from non-motor parts and made to step where researchers choose.

Tumbleweed supplies that proof, assembled from pieces that individually go nowhere.

As a working model, Tumbleweed lets the field test how nanoscale motors trade speed against energy efficiency. That is only the near-term use.

It also sets up a longer effort toward machines that could one day carry molecular cargo through synthetic systems. That mirrors how kinesin and myosin already move materials inside living cells.

The study is published in the journal Nature Nanotechnology.

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