Tuesday, April 28, 2015

The 'Silly Walk' of a Motor Protein is Revealed

Monty Python's Ministry of Silly Walks has a new addition: the pivoting gait of a motor protein that transports cargo throughout the cell. This walk has been imaged by researchers at the University of Oxford, who first had to develop a new high-speed imaging technique.

Cells rely on a transport system to move cargo in, out, and around the cell. This intracellular highway is made up of long protein chains known as actin filaments. Motor proteins such as myosin 5a walk along the actin "roads", carrying various organelles throughout the cell. Because myosin proteins are only a few tens of nanometers in size and because they move very rapidly across the actin, it has been impossible until now to decipher their walking pattern.

This video replicates the rigid walk discovered by the Oxford group, here modeled with flying sweets, pliable balls, and climbing gear (with two nuts acting as the myosin). The protein pivots compass-like over the actin filament in fixed increments of 74 nanometers, binding to the filament with each step.



Previously, scientists thought that motor protein "legs" randomly searched in all directions until they happened to latch onto the actin. But the real walking pattern seems to be much more efficient, according to Philipp Kukura of the University of Oxford who led the new research.

Kukura describes the motion as being similar to walking across the tops of evenly-spaced traffic bollards. "Imagine you had to walk on them and whatever leg is moving is doing a three-dimensional search in space, it's very difficult to find the next one," said Kukura. "But if you keep the angle between your legs the same and you just rotate, you will automatically get to the next one."

Image cropped from Henry de Saussure Copeland via flickr


















The visualization of this walk - based on a new imaging technique that enabled them to take a near real-time movie of the motor protein in action - has been ten years in the making.

"In the macroscopic world, things usually don't move so quickly, so your iPhone camera is able to capture pretty much everything that happens," said Kukura. "But when you go to the nanoscopic world, things just move a lot faster."

In order to witness the protein dynamics, the group developed a camera that can capture nanometer-scale motion with more than a thousand frames per second. This is about a thousand times faster than current small-scale imaging techniques at the same level of precision, according to Kukura.

This high-speed technique is made possible by scattering light off a biological sample instead of relying as before on the sample (or a chemical tag) glowing from fluorescence.

"When you're using light scattering you always get a percentage of the light back," said Kukura. "So if you want to look faster or more precise you just have to send more light in and everything scales. But when you use fluorescence you cannot do that because there's a fundamental limit to how much light a molecule can emit."

This new insight into how biological motors walk on small scales could improve the design of nanoscale machines currently being developed by researchers around the world.

"Before our discovery people might have thought that artificial nanomachines could rely on random motion to get around but our work suggests this would be inefficient. This study shows that if we want to build machines as efficient as those seen in nature then we may need to consider a different approach," said Kukura in a recent article for the Oxford Science Blog.

This work was published last month in the journal eLife.

--
By Tamela Maciel, also known as "pendulum"

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