Creating A Reversible Molecular Motor

New principles could pave the way for custom molecules.
Creating A Reversible Molecular Motor

Tiny molecular motors haul biomolecules and other things around cells.

Dave Zobel, Contributor

(Inside Science) -- A team of biophysicists has produced a molecule-sized motor with an optional "reverse gear." As a result, the field of synthetic biology, in which biological molecules are used as components in the engineering of biological and non-biological systems, has taken an important step forward.

"The basic design of controllable biomachines may not be as difficult as one might have expected," concluded senior researcher Ken’ya Furuta of Japan’s Advanced ICT Research Institute, in Hyogo, Japan, explaining how his team successfully modified an existing molecular motor to run both forward and backward. He presented the research at a meeting of the Biophysical Society in Los Angeles in February.

How it works: Molecular motor edition

Molecular motors typically contain tens of thousands of atoms and run on chemical energy extracted from the ATP (adenosine triphosphate) molecules found throughout cells. One such motor, powered by proteins called kinesins, is able to pull itself along the cytoskeleton, a network of slender microtubules criss-crossing the interior of the cell like a fistful of tiny one-way streets.

A molecule of kinesin – from the Greek root kin-, meaning "motion" -- consists of a long stalk linked by a flexible joint to a globular "head." As with all molecules, different regions on the kinesin head possess different local electric charges. ATP interactions lead to fluctuations in these charges, causing the head first to bind electromagnetically to a nearby microtubule, then to release from it and bind to it again slightly farther along.

The heads of two entwined kinesins can work in concert to produce a progression reminiscent of walking, at speeds measured in nanometers per second. A computer-generated representation of a kinesin pair making its way along a microtubule can be seen in the video "Kinesin Walking Narrated Version for Garland."

Rob Phillips, professor of biophysics and biology at the California Institute of Technology in Pasadena compares this cooperative action to a team of Navy SEALs.

"Each team member is a talented individual," he said, "and yet the only way they can carry a rubber raft is by banding together."

Tinkering with dynein

Technically, the object of Furuta’s interest is not kinesin but the related molecule dynein –from the Greek root dyn-, meaning "power." His team created a dynein-based motor with the ability to manipulate filaments of a material called actin, which they did by grafting a fragment of an actin-binding protein onto the core of a dynein molecule. During testing, they discovered that by slightly altering the orientation of those two components, they could make the motor run in reverse.

That’s a valuable contribution to synthetic biology, said Phillips. "Molecular motors are critical components of the engineering of nanoscale systems," he explained. "If you wanted to send a tiny payload somewhere, you could imagine laying down organic 'railroad tracks' and driving your cargo around on them using controllable, reversible motors."

But the path toward this improvement wasn’t necessarily obvious.

"A molecular motor is an unusual energy converter," commented Furuta, "and the design principles for producing directional movement remain unclear." He credits the recent success to his team’s "bottom-up" approach to the problem.

A reverse approach

In engineering, a "top-down" approach emphasizes analysis, with existing systems being dissected into their major components, which are then further dissected into subcomponents, and so on. By contrast, a "bottom-up" approach uses existing components, even those whose inner workings are poorly understood, as building blocks for new systems. It’s often the case that tinkering gives quicker results than lengthy cycles of deconstruction and reconstruction. Sometimes the best way to build a better mousetrap is just to bolt together miscellaneous pieces salvaged from existing mousetraps and see what happens.

Other creators of novel biophysical machinery are also pursuing this tinker-and-test approach. A team at the University of Chicago analyzed a protein that goes limp in bright light and stiffens in the dark, then grafted it onto a motor protein. The result was essentially a nanoscale motor that could be turned on and off by a beam of light.

Researchers in the field of synthetic biology seek to develop custom molecules that can perform useful functions both inside and outside biological environments. Furuta ultimately aims to design molecules that can provide enhanced methods of communication and computation. His work as a protein biophysicist draws on multiple disciplines -- chemistry, physics, and engineering, among others -- while co-opting elements of biological systems as necessary.

Who’s afraid of biology?

Developments like the reversible molecular motor, said Phillips, highlight the fact that "biology has all kinds of interesting and beautiful specificities." At the same time, he labels as "defeatist" the tendency of many people to dismiss biology as being "overly complicated." For a counterexample, he points to a classic icon of the Industrial Revolution.

"Steam engines are incredibly complex devices, full of flywheels and governors and pistons,” he said. "But once Sadi Carnot, the father of thermodynamics, had identified and distilled out their underlying principles, people started using his elementary physical abstraction to design simpler and more efficient engines. The same thing is now happening with molecular motors. Nature provides these amazing biomachines for converting chemical energy into motion, and trimming down their mechanics to the basics will give us a good starting point for developing our own refinements."

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