What is the connection between a fly’s aerodynamic skill and human heart function? Using the nation’s most brilliant X-rays, located at the Advanced Photon Source at the U.S. Department of Energy’s Argonne National Laboratory, a cardiac molecular motors expert from the University of Vermont (UVM) and colleagues from the Illinois Institute of Technology (IIT) and Caltech performed research to answer that and other questions.
The research team, including David Maughan, Ph.D., research professor of molecular physiology and biophysics at the UVM College of Medicine, published their results in a report in the Jan. 20 issue of the British journal Nature.
To conduct their research, Maughan and his IIT and Caltech colleagues merged extremely bright X-ray beams and a “virtual-reality flight simulator” for flies, designed by Michael Dickinson of Caltech, to probe the muscles in a flying fruit fly and examine how it generates the extraordinary levels of power that result in flight.
The intense X-rays allowed the researchers to identify changes in the crystal-like arrangement of molecules responsible for generating the rapid contractions of the fly’s muscle with a resolution of 6/10,000th of a second. The flight simulator, which fools a tethered fly into thinking it is flying freely through the air, is necessary to produce a stable pattern of wing motion and enabled the team to capture X-ray images at different stages of muscle contraction. By combining the technologies, the researchers could reconstruct a ‘movie’ of the molecular changes in the powerful muscles as they lengthen and shorten to drive the wings back and forth 200 times each second.
“At the molecular level, the insect’s flight muscle and a human heart are remarkably similar,” Maughan said. “We biologists have always been amazed by how hard these muscles work. Now we have taken advantage of the fruit fly’s small size and shone light right through the whole animal, illuminating the working muscles during flight and probing the molecular motions deep within the muscle cells.”
These experiments uncovered previously unsuspected interactions of various proteins as the muscles stretch and contract. The results suggest a model for how these powerful biological motors turn “on” and “off” during the wingbeat.
“Small flying insects face an enormous task — generating enough power to overcome gravity, air resistance and drag — and they do this by beating their wings ferociously,” said Maughan. “We found out that timing is key, where certain molecules have to be positioned exactly with respect to others during each phase of the wing beat in order to produce the high power output.”
The researchers note that the many similarities between insect muscle and other oscillatory muscles, including human cardiac muscle, mean that the research may be adaptable for other uses.
“Both insect flight and human heart muscles store energy during each beat that is later used to help flap the wings or expand the heart after contraction. We found that flying insects store much of the elastic energy in the protein filaments themselves, which minimizes the power costs,” Maughan said.
A previous publication by Maughan and Tom Irving of IIT demonstrated the feasibility of taking movies of molecular changes in live flies. UVM’s Instrument and Model Facility (IMF), directed by Tobey Clark, built a rotating shutter used in the earlier experiment. IMF scientists Carl Silver and Gill Gianetti fabricated the high-speed device.
“How the fly’s muscles turn off and on at 200 times a second has been a mystery that we now can solve in detail using these new technologies” Maughan said.
Maughan and his colleagues’ research experiences with genetically malleable fruit flies has increased the potential for addressing much more specific questions about the roles of various protein components in muscle function using mutant or genetically-engineered flies. Currently, Maughan is collaborating with Jim Vigoreaux, Ph.D., associate professor of biology at UVM, and Doug Swank of Rensselaer Polytechnic Institute, to determine what parts of the flight muscle proteins are responsible for the high speed.
Collaborators on the X-ray project, in addition to Dickinson and Maughan, are Gerrie Farman, Tanya Bekyarova and David Gore of IIT, and Mark Frye of Caltech.
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