Stanford Bioengineers Create Remote-Controlled Nanoscale Protein Motors

Stanford bioengineers create remote-controlled nanoscale protein motors

A team led by Assistant Professor Zev Bryant builds molecular motors to further the study of cell function.

In every cell in your body, tiny protein motors are toiling away to keep you going. Moving muscles, dividing cells, twisting DNA – they are the workhorses of biology. But there is still uncertainty about how they function. To help biologists in the quest to know more, a team of Stanford bioengineers has designed a suite of protein motors that can be controlled remotely by light.

"Biology is full of these nanoscale machines that can perform complex tasks," said Zev Bryant, an assistant professor of bioengineering and leader of the team. "We want to understand how they can convert chemical energy into mechanical work and perform their specific tasks in cells."

Bryant's team, including doctoral student Muneaki Nakamura, designed blueprints for protein motors that would respond to light. Splicing together DNA from different organisms such as pig, slime mold and oat – the oat had the light-detecting module – the bioengineers created DNA codes for each of their protein motors.

Assistant Professor Zev Bryant and his team are creating tiny protein motors that can be controlled remotely by light. (Linda A. Cicero / Stanford News Service)

The remote-controlled nanomotors are described by Nakamura, Bryant and their colleagues in a paper that appeared online Aug. 3 in Nature Nanotechnology.

When exposed to light, the new protein motors change direction or speed. "It's pretty fine spatial control; you can decide where the light is and where it isn't and control motors in this very exquisite way," Bryant said. Being able to control the motors in real time should be a boon for cell and developmental biologists trying to study forces and motion in living things.

"It's an entirely new project for us to be moving inside cells and organisms, and to be working more closely with biologists," Bryant said. Now that he and his team have a basic blueprint, they will be able to customize these motors for biologists who are looking into specific tasks.

"In a future phase of our research, I hope that we can provide cell biologists with tools that allow them to change very specifically the properties of molecular motors in their cellular contexts," Bryant said.

Protein filaments (labeled in green and red) glide on the surface of a microscope coverslip, their motion driven by engineered molecular motors. The motors shift gears when illuminated with blue light, causing the motion to slow down. (Video: Bryant Lab)

There's also the possibility of using the controllable motors outside of biology, in diagnostic devices, for example. Bryant noted that researchers have worked on harnessing molecular motors to perform functions similar to their biological roles, "transporting molecules, sorting molecules, and concentrating molecules."

But first and foremost, Bryant is rebuilding these motors – incorporating features never before seen in biology – in an effort to illuminate their true nature.

"Evolution takes a basic design and makes motors that are fast and motors that are slow and motors that move long distances," Bryant said. "We've tried to build diverse motors and really challenge our understanding by pushing ourselves outside of what's already been done by evolution."

Shara Tonn is an intern at the Stanford News Service.

Tuesday, August 5, 2014

ORIGINAL: Stanford
By Shara Tonn

DNA Motor Transports Cargo Along Carbon Nanotube

Illustration: Tae-Gon Cha/Purdue University

DNA nanotechnology has become one of the great hopes of molecular manufacturing in which large-scale objects could potentially be assembled from the most basic building blocks, atom-by-atom. Research is slowly revealing that many of the assumptions about DNA manufacturing are accurate, such as the ability of meeting design specifications down to atomically precise accuracy.

In the latest development for DNA manufacturing, researchers at Purdue University have developed a DNA motor that can transport nanoparticles up and down a carbon nanotube. While protein-based motors are doing this all the time in biological systems, the DNA the researchers have developed marks the first time that a synthetic molecule has been used to accomplish the same feat.

The DNA-based motor does not travel as fast as a protein-based motor does, but it does have the benefit of being controlled, of operating outside its natural environment and can be switched on or off.

The research, which was published in the journal Nature Nanotechnology (“A synthetic DNA motor that transports nanoparticles along carbon nanotubes”), demonstrated that DNA enzymes could transport cadmium sulfide nanocrystals along the length of a single-walled nanotube, deriving energy to carry its cargo by eating up RNA left along its path.

"Our motors extract chemical energy from RNA molecules decorated on the nanotubes and use that energy to fuel autonomous walking along the carbon nanotube track," said Jong Hyun Choi, a Purdue University assistant professor of mechanical engineering, in a press release.

The DNA enzyme has a core and two arms that come out from the top and bottom of the core. Movement of the DNA occurs as that core of the DNA enzyme cleaves a strand off the RNA. After one strand of RNA has been sliced off, the upper arm of the DNA enzyme grabs onto another strand of RNA and pulls the entire body along.

When the researchers concede that the DNA is slower at moving then their protein-based counterparts, they aren’t kidding. It took 20 hours for the DNA motor to move down the length of the carbon nanotube, which was several microns long.

While the researchers believe that increasing the temperature and acidity of the environment could speed up the process, it’s not clear how much they could speed it up.

It’s also not clear how RNA will always be around to help DNA motors to travel around in different environments. While molecular manufacturing adherents will no doubt be encouraged by this research, we may not need to worry about “grey goo” overrunning our planet as nanobots go about eating everything up to feed themselves.


ORIGINAL: IEEE Spectrum
By Dexter Johnson
Posted 19 Dec 2013 | 21:14 GMT

A Moving Kinesin Motor Protein

ORIGINAL: The Cell: An Image Library - Image CIL:8082

A Moving Kinesin Motor Protein 
The two heads of the kinesin dimer work in a coordinated manner to move processively along the track. The coiled coil (gray) extends towards the top and leads up to the kinesin cargo.
Each catalytic core (blue) is bound to a tubulin heterodimer (green, beta subunit; white, alpha subunit) along a microtubule protofilament (the cylindrical microtubule is composed of 13 protofilament tracks). To adopt this position, the neck linker points forward on the trailing head (orange; neck linker next to but not tightly docked to the core) and rearward on the leading head (red).

ATP binding to the leading head will initiate neck linker docking. Neck linker docking is completed by the leading head (yellow), which throws the partner head forward by 160 angstroms (arrow) toward the next tubulin binding site. After a random diffusional search, the new leading head docks tightly onto the binding site, which completes the 80 angstrom motion of the attached cargo.

Polymer binding also accelerates ADP release, and during this time, the trailing head hydrolyzes ATP to ADP-Pi.

After ADP dissociates, an ATP binds to the leading head and the neck linker begins to zipper onto the core (partially docked neck indicated by the orange color). The trailing head, which has released its phosphate (Pi) and detached its neck linker (red) from the core, is in the process of being thrown forward.

The surface features of the motors and filaments were rendered by G Johnson (fiVth media: http://www.fiVth.com) using the programs MolView, Strata Studio Pro, and Cinema 4D. Protein Data Bank files used throughout the figures are as follows: human conventional kinesin [prestroke, red: 1BG2], and rat conventional kinesin [poststroke, yellow: 2KIN].

Width of tubulin beta subunit (in green) is approximately 40 angstroms. animation; ATP; kinesin; microtubule; motor protein Movie 2 in: Vale RD, Milligan RA.

The way things move: looking under the hood of molecular motors. Science [serial online]. 2000;288:88-95. Available [subscription required] at:
 http://www.sciencemag.org/cgi/reprint/288/5463/88.pdf

Original resource provided by Ronald D Vale.
Work conducted at Howard Hughes Medical Institute and University of California, San Francisco, CA (RV), Scripps Research Institute, La Jolla, CA (RM).

Biological Sources Cellular Component kinesin complexmicrotubule

Biological Context Biological Process ATP catabolic process

Molecular Function kinesin binding

Attribution Names
Ronald D Vale
Ronald A Milligan
Graham Johnson
Pubmed 10753125

Imaging
Image Type animationcomputer graphic

Processing History
surface rendering

Dimensions

Spatial Axis	Image Size	Pixel Size
X	320px	0.118nm
Y	240px	0.118nm
Time	39 sec	12 frames/s