The Physics of Metastasis
Much has been learned about cancer using a flat-bottomed petri dish and growth medium. But this decidedly artificial environment has yielded few clues to the big question, the Holy Grail of oncology research: how do cancer cells break away from a tumor and spread to other parts of the body? It is metastasis, after all, that is responsible for most cancer death.
It’s a question that has caught the imagination of Ryan McAllister, PhD, who is not an oncologist or a biologist, but a physicist in the Georgetown University Department of Physics. Above all, he is a self-described “migrant” scientist who is interested in exploring a wide field of subjects, everything ranging from laser chaos and fluid dynamics to control of such infectious diseases as malaria and HIV in Africa.
Recognizing the complexity of cancer, oncology researchers at leading centers have, of late, drawn on mathematicians, chemists, and physicists, among others, to help solve fundamental biological questions. And that suits McAllister, who loves to develop instruments and assays to help ask difficult questions and to support his foray into biology with a career development award from the National Cancer Institute (NCI). In addition to his work on the campus side, McAllister has become a full member of the Georgetown Lombardi Comprehensive Cancer Center.
He is now working on a prototype assay that more closely recreates the physical universe of a cancer cell, and is part of a team of researchers that includes Susette Mueller, PhD, professor of oncology, Daniel Koch, PhD, a postdoctoral physicist fellow, and Jamie Polackwich, a graduate student in physics.
A far cry from the flat surface of a lab dish, these “machines” offer cancer a 3-dimensional matrix that mimics a living environment.
McAllister conceptualizes the assay this way: “Imagine a spider crawling through a 3D spider web. It has got to manipulate its relationship with the fibers of the web to crawl through them. It has to use force. Now think of a cancer cell as the spider, and the web as fibers of body tissue. The task is to understand the force a cancer cell needs in order to metastasize.”
For the web, the team uses a network of collagen fibers mounted on top of a sheet of see-through rubbery gel. Embedded in the gel are tiny bead-like tracer particles, so when the cancer cell crawls along the web, pushing and pulling the fibers, the tracer beads move around. The team can measure the force the cancer cell exerts on the beads in four dimensions – distances in length, width and depth, and time – by measuring the bead motion.
A lot of data is generated - a cell migrating for five hours can generate 50,000 force measurements. And in the same way that physicists who study cosmology conceptualize the universe from analyzing how astral bodies move, McAllister’s particular role is to “visualize the data - figure out how we look at it.”
There is an added complexity: the cancer cells being studied express varying levels of two proteins (Src and PKD1) that are known to play a role in metastasis. By measuring the different forces that these migrating cells exert based on expression of these proteins, the researchers aim to understand the proteins’ precise contribution to metastasis. Based on a pilot study, McAllister suspects that Src controls how hard a cancer cell pushes against its web in order to migrate, and that PKD1 has a complicated role in directing motion.
McAllister says he is energized by his work at Lombardi.
“No way am I smarter than the oncologists I work with,” McAllister says. “They do a lot of things I could never do. But I can perhaps think of an interesting approach to a problem, and I can build machines.
“And that means I have my hand in trying to solve a long-standing biological problem,” he says. “And that is both fun and rewarding.”
By Renee Twombly, GUMC Communications