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.

My passion: Understanding science

I shared the following column, which ran on March 11, 2013, as part of the "My Passion" series in our local newspaper. 

Growing up in Las Vegas with parents that insisted I venture out into summer’s sandy oven, I spent a lot of time catching scorpions, vinegaroons and all kinds of reptiles. I marveled at the way each creature seemed perfectly suited for its place — and its prey. 

I’ve seen blood squirt from the eyes of a horned lizard, and I’ve dropped a desert iguana when distracted by the whip of its separated, writhing tail. One of my best friends can attest to the wallop a small sidewinder packs.  

Despite all the time I spent exploring and experiencing the desert, it wasn’t until a college trip with friends to Zion National Park, far from the electric skies of Las Vegas, that I looked up and saw the Milky Way - the band of stars that form the “backbone of night.” I felt the bewildering immensity of nature for the first time.

I still wonder what our ancestors thought as they gathered around a fire pit and looked to the sky. Some of their answers became myths that shaped and were shaped by society, but what of the countless millions who weren’t satisfied by such explanations? Among the everyday struggle for survival, there must have been people like me — people for whom the echoing question, “What are stars?” would never be silenced.

Human nature is to seek understanding. Our minds are powerful, complex but imperfect pattern detectors. When we look at clouds, we see shapes. We impose meaning on randomness. We confuse correlation and causality. We infer intent by default, and because we are biased to reinforce our own beliefs, it takes effort to overcome an incorrect idea that has taken root. 

These biases served us well through millennia. We survived. 

Through science, we’ve opened a window to the heavens, and we’ve looked back in time to discover much about how we came to be. 

I was stunned to learn that nearly half of Americans don’t know how long it takes our planet to revolve around the sun. I cringe when politicians deny evolution. My heart breaks when children die from easily preventable or treatable conditions because parents decide against vaccines or choose prayer over medicine.

Though science has certainly demonstrated its value to our health, economy and quality of life, it is more than advanced technology or medical treatments. The scientific method is humanity’s best tool to discover truth.

I started the local Science Pub series in conjunction with OMSI, and I collaborate with scientists to help share their work with the public. I’m passionate about the public understanding of science not just because I love the mysteries of quantum mechanics, neuroscience and cosmology, but because scientific literacy affects our ability to evaluate important issues facing our society.

With our growing population, its commensurate impact, our advancing technological sophistication and proliferation of ideas and claims, we need decision makers who understand the value and methods of science. We need a scientifically literate electorate that is able to face with open eyes our economic, environmental and geopolitical challenges.

I’m passionate about the public understanding of science not only because it answers the question, “What are stars?” but because I believe that the truth is the best foundation upon which to build our future.

Professor's journey shapes student experience

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.”