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The Physics of Rapidly Spreading Cancer

The Physics of Rapidly Spreading Cancer
Using a computer simulation that models the physical and chemical interactions of cancerous cells (colored dots), researchers discovered that over time, tumors develop a distinctive two-part structure: slow moving cells moving randomly in a dense core (blue and purple), surrounded by a band of cells moving faster and more directly outward (green, yellow, red). Arrows indicate direction of motion. The image at right is the same tumor cut in half to reveal the inner structure. Image credit: Anne Bowen, Texas Advanced Computing Center at the University of Texas at Austin.

Scientists have recently discovered a method in cancer's madness. Before now, they've been perplexed by how cancer cells, growing alongside healthy cells, often spread much faster into surrounding tissue than randomness would dictate. It's as if cancerous cells are intentionally moving directly outward, invading healthy tissue.

Scientists have struggled to explain this behavior from a biological perspective. Now a team of chemists and physicists from The University of Texas at Austin have used a computer simulation to explain, for the first time, the physics driving this motion.

The computer model simulated the early growth of a tumor, so what begins with 100 cancer cells results in 20,000 cells, corresponding roughly to about a week's worth of growth for a cancerous tumor. The researchers designed the model to take into account things like the mechanical properties of cancer cells (their stiffness and how likely they are to stick to other cells) and their rates of birth and death.

The team discovered that when cancer cells have the ability to grow and divide much faster than they die, tumors tend to develop a unique spherelike structure with two distinct regions—a dense core of cells that don't grow or divide much and an outer band of cells that grow and divide rapidly. Cells in the core don't have much freedom to move because they are packed together like sardines in a can. Cells on the outside, with a firm foundation below them, are able to move quickly and efficiently outward, like a diver pushing off from a diving board.

Scientists observe this same kind of motion, called superdiffusion, in bubbles moving in foams. Before this study, researchers had no reason to believe that cancer cells would behave the same way.

The results appear online in the April 27 edition of the journal Physical Review X.

Along the way, the researchers also found that this two-part structure—dormant cells in the core and active cells on the periphery—arises at very early stages in the growth of a tumor, driven by cell-to-cell forces. Other researchers have observed the emergence of such two-part structure in so-called in vitro experiments, involving cell cultures in a dish or in three dimensional wells, but they have focused primarily on nutrient or oxygen depletion while the contribution of mechanical aspects of the cell has so far been underappreciated.

That two-part structure is a simple form of what researchers call heterogeneity—when cells aren't identical across the whole tumor. It can refer to variations in either behavior or genetics of cells from place to place.

In recent years, scientists have come to understand that one of the reasons cancers are so hard to treat is that over time, they evolve into a complex mix of different types of subpopulations all within the same tumor. And not all subpopulations respond the same to treatments.

"In a sense we are providing insight into when and how heterogeneity comes about and that could be helpful in trying to develop strategies to prevent heterogeneity," said Abdul Malmi-Kakkada, a postdoctoral researcher who led the project, along with postdoctoral researcher Xin Li, and professor and chair of chemistry Dave Thirumalai.

Prior to the new study, most researchers assumed cancer cells spread somewhat randomly, like a drunk person walking.

"People imagined that these cells will take a step to the right, then a step to the left," said Malmi-Kakkada. "Even though they want to move forward, they will move in a zigzag way. That's undirected movement. It's very inefficient."

Instead, in the UT Austin simulation, cancer cells on the outer edge of a tumor act like sober walkers with a concrete goal of moving in a straight line from point A out to point B. This behavior arises not from some intentionality on the part of the cancer cells, but rather from the physical and chemical rules that govern these small particles. Himadri S. Samanta, a postdoctoral researcher in the Department of Chemistry and co-author on the new study, developed a novel theory explaining how superdiffusive motion can come about.

Watch a video illustrating some of the key findings from the simulation:

Just as the study of the physics of biological systems has inspired engineers to create materials that stick without adhesive (Velcro was inspired by burrs from the burdock plant), wind turbines that can spin faster and more safely (by adding bumps to the blades like those on whale fins), and more efficient water desalination systems (based on water filtering proteins found in all living cells), physical scientists hope their expertise can shed light on some of the most intractable problems in the life sciences.

"Having a physicist working on cancer can provide a new perspective into how a tumor evolves," Malmi-Kakkada said. "And rather than only looking at genetics or biology, trying to attack the problem of cancer from different perspectives can hopefully lead to a better understanding."

The paper's other author is Sumit Sinha, a graduate student in the Department of Physics.

This research was funded by the National Science Foundation.

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Tuesday, 28 March 2023

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