Stanford scientists genetically engineer versions of myosin proteins that transport biological materials in cells to illuminate design features that keep these protein motors on track. Inside our cells, proteins known as myosins can act as a delivery service for biological materials. To better understand how molecular motors move, Stanford bioengineers have built experimental versions of the proteins, changing the way these transporters get around. Led by Zev Bryant, an assistant professor of bioengineering at Stanford, a team of researchers has genetically engineered “mutant” myosins with new features such as gearshifts and improved traction. The group’s most recent findings are published in the January issue of Nature Nanotechnology, where they are highlighted alongside other studies of molecular motors.
“You look at biology, and you see motors that have diverse mechanical properties, and you want to understand how these arise,” Bryant said. “You test your understanding by trying to build something new.” Molecular motors are a class of proteins that make up the moving machinery of cells. Myosins are one family of molecular motors. Some of them can shuttle biomolecules from one region of the cell to another.
These myosins move along microscopic filaments made of the protein known as actin. These actin filaments are one component of the cytoskeleton, or internal support structure of the cell. Bryant wanted to test his understanding of how evolution has designed these myosin proteins to shuttle cellular freight. Funded by an NIH “New Innovator” Award, members of the group launched a series of experiments in 2008 that steered their myosin research in a new direction. They began engineering myosins with extra parts to give natural myosins new capabilities.
Natural myosins, for example, see actin filaments as one-way tracks. To better understand this one-directional motion, Bryant challenged his group to design mutant myosins that could move forward and backward on command. The researchers engineered myosin motors with extra components that behaved like a molecular gearshift. In a 2012 Nature Nanotechnology report, the researchers showed that they could shift their mutant myosin motion between forward and reverse. However, these two-way myosins had trouble hanging onto their actin tracks.
“When we engineer motors to have new capabilities, we often sacrifice some capabilities that they already had,” Bryant said. So the group focused on creating motors that excelled at hanging on.