Be it a paper cut or a surgical incision, whenever we are wounded, cells work together to heal our bodies. To do so, cells must move, and Jacob Notbohm wants to understand how.
Notbohm, an assistant professor in the Department of Nuclear Engineering and Engineering Physics, has received a three-year, $345,000 National Science Foundation grant to study the forces that dictate cellular motion.
His research has various potential applications ranging from cancer prevention to wound healing. “You’d expect that if cells could move more freely and quickly, they’d be able to heal wounds faster,” says Notbohm.
In his research, Notbohm uses a unique combination of methods to investigate how contractile force and adhesion energies interact in the same experiment. He then compares his experimental data to a theoretical model that predicts how small changes in some variables, including force and adhesion, can have big effect on motion.
Contractile forces within cells result from structural proteins that change shape, causing them to shorten. The force generated by such contraction pulls the cell forward. In this way, a cell moves a bit like an inchworm that contracts its body to pull its rear along as its front extends forward.
On the other hand, adhesion energy is generated when cells come into contact with other cells or materials. If they stick well, like tape to a wall, there is a positive adhesion energy—and pulling them apart, like peeling tape off a wall, uses energy.
In a purely mechanical system like tape stuck to a wall, force and adhesion are completely separate concepts. For cells, however, force and adhesion may be coupled because some of the same proteins responsible for force are also responsible for adhesion. Further complicating matters is that cells are active—they generate their own forces, making it difficult to sort out the complicated relationship between force, adhesion, and motion.
To measure the forces of interacting cells, Notbohm puts them on a soft surface that deforms like Jello in response to the cells’ forces. Then he uses optical microscopy and quantitative image analysis to track how the gel-like surface deforms as the cells migrate, and ultimately, to compute the cellular forces.
With that information, Notbohm tests predications made by a theoretical model, which will provide needed data to advance the model as well as our understanding of cellular motion.
He seeks to reveal how small changes in one variable could act like a switch that activates mobile, wound-healing behavior. “It’s rewarding to see theoretical predictions play out in the lab,” he says.