Researchers Discover Cell Migration Works Beyond Force Generation
A professor specializing in mechanical engineering and materials science has discovered that cell groups can move more quickly with less force when they are attached to soft surfaces that have aligned collagen fibers.
In the field of mechanobiology, it has long been assumed that the forces exerted by cells are crucial for their effective functioning, including rapid movement. However, a team at the McKelvey School of Engineering at Washington University in St. Louis has challenged this notion by demonstrating that cells can migrate faster while generating reduced force, undermining the traditional view on the role of force in cell movement.
Amit Pathak’s lab, where he serves as a professor, observed that clusters of cells can move more than 50% quicker on surfaces with aligned collagen fibers when compared to random fiber arrangements. Previously, cells were understood to create continuous forces to combat friction and drag in their surroundings. Yet, this traditional requirement for force appears to be diminished under optimal environmental conditions, such as when fibers are aligned. This significant finding, published in PLOS Computational Biology on January 9, marks the first time such behavior has been documented in collective cell migration.
For years, Pathak and his research team have been studying the movement patterns of human mammary epithelial cells. They found that cells tend to move faster on rigid surfaces but struggle on softer ones, leading to delays in their movement. Their findings have potential implications for understanding cancer metastasis and healing wounds.
In the recent study, researchers confirmed that cells migrated significantly faster on structured collagen fibers than on disorganized ones. Moreover, it was observed that these cells relied on the aligned fibers as directional indicators to facilitate their collective migration.
Pathak noted, “We were curious if cells could maintain high speeds without generating more force in the absence of friction. Our conclusion was that the environment plays a crucial role. We initially anticipated quicker movement on aligned fibers, akin to how trains use tracks, but were surprised to find that the cells were exerting less force while still moving faster.”
Amrit Bagchi, a former doctoral student in Pathak’s lab who completed his Ph.D. in mechanical engineering in 2022, contributed significantly to the research. During the COVID-19 pandemic, he meticulously developed a soft hydrogel in Marcus Foston’s lab, an associate professor of energy, environmental and chemical engineering. He aligned the fibers using a special magnet at the School of Medicine before placing the cells on the hydrogel to monitor their movement.
Bagchi crafted a layered motor-clutch model, where the cells’ force-generating mechanisms acted as the motor, while the clutch provided traction. He adapted this model for collective cell behavior by incorporating three layers: one for the cells, another for the collagen fibers, and a third for the gel beneath, ensuring that all layers interacted seamlessly.
“The experimental outcomes initially took us by surprise,” Bagchi stated. “However, these findings motivated us to create a theoretical model that explains the physics behind this unexpected behavior. We gradually realized that cells treat aligned fibers as a form of frictional resistance, which operates in a notably different way than in cases with random fibers. Our model’s principles of matrix mechanosensing and force transmission also anticipate other recognized behaviors in collective migration, such as haptotaxis and durotaxis, providing a cohesive framework for researchers to investigate and potentially apply to other intriguing cell migration issues.”
