11/15/2022
By Brooke Coupal

A research team led by Biological Sciences Asst. Prof. Nicolai Konow will work across disciplines to develop a deeper understanding of how muscles function.

Funded by a three-year, $2.14 million National Science Foundation (NSF) grant, the research team, which also includes Chemistry Assoc. Prof. Matthew Gage, Biological Sciences Prof. Jeffrey Moore and Sam Walcott, an associate professor of mathematical sciences at Worcester Polytechnic Institute, will study bite performance in rodents using a multi-scale approach, meaning they will examine everything from molecules to the full muscle and skeletal system.

“Everything has to be broken down to its building blocks,” says Konow, who is the principal investigator for the grant. “We think many problems that come with understanding muscle are due to cell-molecular and organism-scale researchers not having easy access to an exchange of ideas and knowledge, which we will have.”

The researchers will test if bite performance is influenced primarily by muscle size and shape, skeletal geometry or the presence of masticatory myosin – a fibrous motor protein found in the jaw muscles of some animals. 

“This is an evolutionarily ancient myosin, and there have been some reports that it is superstrong and superfast,” Moore says.

These reports challenge the typical force-velocity tradeoff of muscles, which states that muscles generate high force at slow speeds and low force at fast speeds. To understand how masticatory myosin functions, the researchers will look at its molecular properties and how this links to the whole muscle.

“The more we understand the molecular details of what makes myosin function, the better we’re going to understand muscle function,” Gage says.

Insights gained about masticatory myosin through this study will help determine why some species have this myosin, like sharks and gray squirrels, and others do not, like humans and rats.

Gage will be producing masticatory myosin in his lab using muscle cells. He will infect the cells with a virus that will hijack the cell machinery and subsequently produce the myosin.

“We let that go for a certain period of time, and then we can break open the cells and recover the myosin from there,” he says.

The masticatory myosin is then purified before being sent to Moore’s lab, where he will be comparing masticatory myosin to other skeletal muscle myosins that have been well-characterized.

Image by Pixabay

“We’ll look at their properties at the single-molecule level, and then we’ll look at them at the multiple-molecule level,” Moore says.

Through a testing system known as the in vitro motility assay, Moore will be putting myosin molecules on glass slides before introducing the molecules to actin, another protein found in muscles. From there, he can observe how the two proteins interact.

“With the purified molecules, we’re able to reconstruct some of the basic properties of muscle contraction, so we can see the speed and force with those,” Moore says.

Two rodent species that Konow will be studying are red and gray squirrels, the latter of which has masticatory myosin. He will examine how the myosin impacts rodents’ bite performance in addition to looking at other factors like muscle size, skeletal geometry and bite type.

“A potential outcome is you might have muscles that have this superfast or superstrong myosin in them, but when you place those muscles into the context of the feeding apparatus, the way they’re attached in there and the sheer size of them might be much more important in determining if a rodent can crack its nut or not,” Konow says.

Data gathered from the labs of Gage, Moore and Konow will be given to Walcott, who is serving as the multiscale mathematical muscle modeler. He will take the information and put it into predictive models to link force-velocity properties from the molecular scale to the physiological scale to determine the feeding abilities of rodents.

“One of the big strengths of this proposal is the modeling approach, where we’re incorporating data from all scales to try and understand how these properties interact in this complex environment,” Moore says.

The findings of the research can aid scientists in understanding muscle illnesses in humans by looking at how myosins govern force and velocity.

“Muscle illnesses often have to do with myosin, so when we learn what the different isoforms are capable of, it will inform therapies,” Konow says.

As part of the grant, the research team plans to create a computer game that will teach high school students about the biology of muscle. The game will be a bite-force challenge where they are given an item like a nut and must manipulate different properties, such as muscle size and protein content, to successfully crack it.

“This interaction with STEM novices is exciting and can be really fruitful to us scientists, because it’s often the inexperienced eye that sees the problem clearer than someone who stared themselves blind to it,” says Konow.