Looking Under the Hood

Physicist David Altman is moved by myosin. We all are.

Myosin is a motor protein. Responsible for every conscious and unconscious flex of our muscles, it beats our hearts.

Altman wants to understand how the molecular motor works — how the roiling action inside of a cell affects myosin's function. In 2012, Altman spent his junior sabbatical at McGill University in Montreal, Canada, performing an experiment that tested competing theories about muscle fibers’ unusual mechanical properties. The results of his experiment were published April 16 in PLoS ONE.

Muscles and Motors

Muscles have an odd and poorly understand behavior. Normally, an active muscle is stiff, because its proteins interact and form connections. But when an active muscle is used in a cyclic fashion — think of your heart beating or leg muscles when you’re running — the muscle temporarily becomes softer. When the cyclic motion stops, the muscle stiffens again.

This temporary softening, called thixotropy, may be connected to our posture. Stiff muscles provide support when you sit in class, but become less stiff and more limber when you run. The mechanism of thixotropy in muscles is not well understood, though Altman suspected that myosin was the key.

At the heart of muscle fibers are two types of interlocking filaments: myosin filaments — which contain hundreds of myosin motors that tie themselves together — and actin filaments. In active muscle, myosins bind to actin. Myosins make muscles contract by pulling themselves, stroke by stroke, along the actin filament.

Loosening Up

Altman wanted to test whether the interaction between actin and myosin was responsible for muscle’s thixotropy. According to this model, muscles’ cyclic motion breaks the actin-myosin attachments and makes the muscle fiber softer. Once motion stops, it takes a little while for myosin to re-bind to actin and make the fiber stiff again.

Altman’s experiment involved disrupting actin-myosin interactions and vibrating the muscle fiber at different frequencies to measure its stiffness. Using two chemicals that prevent myosin binding to actin, Altman then tested the muscle. The loosening effect vanished.

“To people who study muscle, it was a debate as to what was responsible for thixotropy,” says Altman. ”The experiment indicates that muscles’ stiffness depends on myosin’s grip.”

Next Steps

The experiment revealed another, unknown process at work. When the cyclic motion was slow enough, Altman was surprised to find that the muscle fiber no longer softened; it became stiffer, or rheopectic. Altman suspects thixotropy depends on forces from molecules jostling within the crowded cellular environment, but no one knows how or why muscles would stiffen when subjected to low frequency vibration.

Through Willamette’s Senior Research Seminar course and through the Science Collaborative Research Program, students work with Altman to learn more about myosins’ cellular function. “In my lab, we study myosins inside cells as opposed to just purified myosins, because we want to understand physiologically relevant conditions and how they affect the motor,” says Altman.

Over the summer, he’ll move his myosin-trapping laser lab to the basement of Collins Science Center. In the fall, Altman will continue working with physics majors on their theses, while looking for more collaborative research opportunities to explore the enigmatic muscular motor protein.

Professor's journey shapes student experience

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Photo by Frank Miller

David Altman described his first year teaching as more exciting than he could have imagined. It was punctuated by two nationally competitive grants to study the protein myosin, a family of motor proteins that are core pieces of cellular machinery.

When you clicked on the link to read this story, myosin was at work. It is the cell’s motor, responsible for muscular contraction among many other cellular functions.

“Myosin’s got this elegant simplicity,” Altman said. “I want to understand how the motor works.”

Collaborative research

As part of Willamette’s Science Collaborative Research Program, Altman works with Jared Green ’11 and Jesse Sant ’12. The team spent the summer building an optical trap in Collins Science Center, using a laser to examine myosin’s behavior. They will analyze the motor’s range of motion and perform experiments to study its function in retinal cells.

“I’m really excited to use the lab for my senior project,” said Green. “David and I sat down and came up with a really cool idea. We’re going to look at how the molecular motor works in endocytosis within eye cells.” Endocytosis is how cells absorb molecules from outside the cell.

“Jesse will use the lab for his junior year ATEP, Advanced Techniques in Experimental Physics, which I’ll be teaching next semester,” Altman said.

The research he and his students are doing now will act as the springboard for future projects, continuing to study myosin not just in its original form but also working to engineer specific behavior. Likewise, Altman would like to see Green’s work become the framework for a model of myosin function within eye cells.

Altman’s journey

Altman’s own intellectual voyage mirrors many students’ college journeys. “I like exploring as many things that I don’t understand as possible,” he said.

“I started working with optical traps as an undergraduate in Chicago, where we studied the dynamics of colloids – the dispersion of small particles in liquids,” Altman said. His optical trap experience paid off in graduate school at Stanford, when he was asked to be part of a biochemistry team. Ultimately his work led to collaboration with a group in India, beginning Altman’s focus on molecular motors in cellular systems.

Altman’s passion for intellectual exploration has influenced his students. The team visited Stanford to create motor proteins using the university’s specialized equipment, and the trip was transformative. “Just sitting in on some of David’s conversations with his colleagues and seeing the immersion you get in grad school where you’re constantly talking and reading about all of these subjects was really cool,” Green said.

Green’s goal is to become an educator, a goal which was well-served by working with Altman through SCRP. “Having a research background and being able to bring a lab to a department would be an advantage,” he said.

Outside the lab

Even the staunchest researchers need a break from the darkened laboratory space required for such optical trap experiments. Altman often meets with students outside of the Collins Science Center to discuss the team’s work or occasionally to jam.

“Willamette has been fun in that you get to form really close relationships with a lot of professors,” Green said. “I first got to know David when we played in a band last semester at Wulapalooza. It was called ‘Dr. Altman’s Bird Refinery,’ and we had a really good time.”

Altman is a percussionist. “We’re looking at playing bluegrass this year,” he said.

When not in the lab or teaching, you might see Altman downtown at Governor’s Cup, Venti’s or Tangled Pearls, a new knitting shop. “Our lab in general has become a big fan of Clockworks Café,” Altman said. “That’s become a regular meeting spot.”

Whether in class, working in a lab or chatting over coffee, Altman appreciates the opportunity to get to know students personally. “The interactions in the small classes at Willamette were so wonderful,” he said. “I definitely ended my first year thinking I’m in the right place.”

Watkins' research presents a challenge for current cosmological model

According to Richard Watkins’ latest research, nearby galaxies have an enigmatic “flow,” like billiard balls rolling on a slightly tilted table – motion that challenges the current cosmological model.

Watkins, a physics professor at Willamette University in Salem, Ore., is at the leading edge of research into the movement of galaxies. He works with Hume Feldman from the University of Kansas and Michael Hudson from the University of Waterloo to use satellite data to draw conclusions about how galaxies flow.

In 2001, NASA launched the Wilkinson Microwave Anisotropy Probe (WMAP), which measures remnant light from the Big Bang. This light loses energy as the universe itself expands. By measuring tiny differences in the resultant low-frequency microwave radiation, WMAP’s precise scans define parameters of mathematical models of the universe.

WMAP image of the universe's matter density at 380,000 years

According to the prevailing model, the expansion of space causes all galaxies to recede from each other. Galaxies also flow towards areas of higher concentrations of mass because of gravity. The model makes very specific predictions about how galaxies should move based on expansion and gravity. Scientists refer to any additional movement as “peculiar velocity.”

Watkins’ team measures this peculiar velocity by directly comparing previous surveys of differing volumes of space from “nearby” galaxies – within 163 million light-years of Earth.

His team calculated that nearby galaxies are flowing quickly, at the very edge of consistency with the prevailing model. “What’s the likelihood that a universe with the WMAP parameters could give us this big of flow?” Watkins asked. “It’s less than 2 percent.”

The simplest explanation for the flow found by Watkins’ team is that we live in a statistically unlikely volume of space. “If you had a hundred volumes, you’d expect one or two out of a hundred to be moving with this velocity,” Watkins said.

A researcher from NASA’s Goddard Space Flight Center, Alexander Kashlinsky, takes Watkins’ results much further. Kashinlisky cites Watkins’ work in a recent article as potential support for Kashlinsky’s notion of “dark flow.”

Kashlinsky’s team uses a different technique to look much further away on a much larger scale. In their latest paper, the team claims to have found evidence of a large flow of galaxies that is in roughly the same direction as the much smaller flow measured by Watkins’ team in nearby space.

While Watkins’ measured flow is improbable but within the bounds of the prevailing model, Kashlinsky’s results would require a major revision. Kashlinsky suggests the flow “might provide an indirect probe of the Multiverse,” a theory that suggests that our universe may be part of a higher dimensional space in which there are many – or even and infinite number of – other universes, potentially with different physical laws.

His results have met with some skepticism in the scientific community. Several physicists have taken aim at Kashlinksy’s conclusions, specifically the way he computes the level of uncertainty in his calculations.

According to Watkins, figuring out uncertainty on such extreme scales is difficult, and his next step is to use computer simulations to test his team’s assumptions. Watkins also expresses some reservations about tying his team’s results to Kashlinksy’s conclusions.

“There may be some process that we don’t understand. Perhaps something that occurred between the Big Bang and now to cause this peculiar velocity, but you don’t need something radical to explain our flow.”

Scientists remain conflicted about the extent, direction and cause of the flow. “We need more data,” Watkins said. “This is an indication that something is not quite right. Right now, it’s just a hint.”