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Truckin’ Molecular Motors: The Tilt and Wobble of Myosin-V

Goldman Biophysical Journal cover Mar 13Never in a million years would I have thought that I’d be writing about blues musician Blind Boy Fuller, cartoonist R. Crumb, and molecular motors in the same blog post. The Popular Science blog and sci-fi future blog io9 took notice first. The cover of last month’s Biophysical Journal likens movement of the molecular motor Myosin-V to the exaggerated, wobbly gait of R. Crumb’s “Mr. Natural” on the cover of Blind Boy Fuller's record album "Truckin' My Blues Away."

There’s even a link to a 1930s Fuller recording on the io9 post. The Pop-Sci post has a great 22 second animation of a kinesin molecule “walking” along a microtubule while dragging its large cargo and another video of Myosin-V’s tilt and wobble on an actin filament.

These all refer to papers recently published by researchers from the Pennsylvania Muscle Institute. The Biophysical Journal cover is an adaption by sci-artist Patrick Lane submitted by Penn scientists.

The labs of senior authors Yale E. Goldman, and Erika L.F. Holzbaur, both in the Physiology department, have been studying molecular motors for close to a combined five decades. Colleagues Henry Shuman, Phillip C. Nelson in Physics, Haim Bau in Mechanical Engineering, Russel J. Composto in Materials Science, and PMI director Mike Ostap round out the team.

They investigate molecular motors -- proteins that function as tiny molecular machines to move cargos within a cell – to get a better handle on what happens when the transport of cellular cargo goes off track and how that may be the start of developmental and neurodegenerative diseases.  

The Biophysical Journal paper details how Myosin-V works in the “harsh” environment of the cell on a nano scale. Myosin-V must function in a sea of water molecules that bombard it 1012 times every second. And what’s most spectacular is that myosin uses this seemingly chaotic environment to adjust its short-lived sub-steps to search for the next binding site on its actin track to keep efficiently moving onward. Literally, myosin V uses its fluctuating environment to extend its reach to take each new step.

 

Goldman, Nelson, and company conduct their observations into this micro world with single purified molecules using custom a fluorescence microscope that Goldman and junior colleagues designed and built to see the detailed tilts and wobbles of molecular motors. He calls this the “bottom up” approach.

The researchers also use super-high resolution cell bioimaging, the “top-down approach.” A related paper recently published in the Proceedings of the National Academy of Sciences uses both approaches to understand how components of cell motility like the cytoskeleton and molecular motors work together. Using optical trapping technology in live cells, they found that different types of molecular motors work as a team to get to their target destination. In the center of cell, dynein and kinesin work on microtubule tracks and switch to myosin on actin tracks at the periphery of the cell. Using immune cells called macrophages, they asked, how the microtubule motors operate together. They found that cargoes simultaneously engage with many microtubules and generate high forces to move back and forth in the macrophages.

These papers illustrate how scientific collaborations across multiple disciplines coupled with development of new biophysical technology facilitate discriminating measurements on complex biological networks, notes Goldman. Both of the papers, he adds, show that molecular motors have also evolved sophisticated collaborative adaptations to conduct their essential transport functions. 

 

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