Cells are the bedrock of life as we know it, carrying out essential biological functions across organisms.
But, as Joshua Brockman is quick to note, cells are also mechanical entities, exerting and sensing physical forces as they try to understand and act on their surroundings. And Brockman is eager to probe those mechanical outputs for clues that could inform and improve healthcare treatments, such as cancer immunotherapy.
Brockman has brought his work at the intersection of mechanobiology and immunotherapy to the University of Wisconsin-Madison, joining the Department of Biomedical Engineering as an assistant professor in fall 2023.
“Very rarely when developing therapies do we think about cells as mechanical,” says Brockman, who comes to Madison after spending three years at Harvard University’s Wyss Institute for Biologically Inspired Engineering as a postdoctoral researcher. “I want to understand mechanical forces in more natural systems, and I want to use them as a design principle to improve therapies across the board.”
Mechanobiology, an interdisciplinary field that hooked Brockman as an undergraduate student at Ohio State University, explores the effects of mechanical forces on cell behavior, development and disease.
As a PhD student at Georgia Tech and Emory University, Brockman built molecular tension sensors out of DNA and other polymers, creating bobby-pin-like probes that translate the mechanical forces exerted by individual proteins on a cell’s surface into light—allowing researchers to see and take images capturing that information. Taking that work even further, he developed techniques to measure the orientations and locations of those receptor forces, which are at the Piconewton scale—roughly one-trillionth the amount of force required for a human hand to hold an apple, Brockman says.
Now, he hopes to leverage those tools to bolster immunotherapy, augmented by the knowledge of the immune system and biomaterials he gained from working in the lab of Harvard Professor David Mooney, who’s a UW-Madison chemical engineering alumnus, Madison native and National Academy of Engineering member.
“I have this deep conviction, backed by the literature, that physical forces are really important in the way the immune system works, including the way the immune system combats diseases like cancer,” says Brockman, whose postdoctoral work was funded by a National Cancer Institute grant. “One of the things that I hope to do is merge mechanobiology with immunotherapy in a way that just really hasn’t been done before.”
For example, Brockman says, the T-cell receptors on the surface of the immune system’s enforcers are mechanically active. But it’s unclear whether the same is true of the recognition machinery on genetically engineered chimeric antigen receptor (CAR) T cells, one of the leading cancer immunotherapies. Brockman hopes to find out and then explore ways to potentially modify receptor mechanical functionality to bolster efficacy of immunotherapies.
He also plans to translate his work measuring cellular receptor forces to viscoelastic surfaces that replicate the human body’s tissues—partially elastic, but also continuing to deform over time under sustained force.
“I don’t feel like we understand very well how viscoelasticity alters the immune system’s ability to execute its functions,” he says. “If you have a tissue that’s both soft and highly viscous, will that really hurt the ability of your immune system to fight off that tumor, for example? And if that’s the case, maybe there’s something we can do.”
At UW-Madison, he’s eager to collaborate with colleagues who are experts on the extracellular matrix that surrounds tumor cells, such as Vilas Distinguished Achievement Professor Pamela Kreeger, and leading imaging researchers like Associate Professor Kevin Eliceiri, Professor Melissa Skala, and Peter Tong Department Chair and Professor Paul Campagnola.
“For me, this was a match made in heaven,” he says.
Top photo by Joel Hallberg