In mechanobiology, cells' forces have been considered fundamental to their enhanced function, including fast migration. A group of researchers in the McKelvey School of Engineering at Washington University in St. Louis has found that cells can generate and use lower force yet move faster than cells generating and using high forces, challenging long-held assumptions about cellular mechanics.
The laboratory of Amit Pathak, professor of mechanical engineering and materials science, discovered that groups of cells moved faster with lower force when adhered to soft surfaces with aligned collagen fibers. Traditionally, cells have been thought to continually generate forces to overcome friction and drag in their environment. However, this conventional requirement for forces can be reduced in favorable conditions, such as aligned fibers. Their findings, published in PLOS Computational Biology on January 9, 2025, represent the first demonstration of this phenomenon in collective cell migration.
Pathak and his lab members have tracked the movement of human mammary epithelial cells for years, establishing that cells migrate faster on hard, stiff surfaces compared to soft surfaces, where they tend to become immobilized. The implications of this research extend to cancer metastasis and wound healing.
In the new study, the researchers found that cells migrated more than 50% faster on aligned collagen fibers than on random fibers. Additionally, they observed that cells utilized aligned fibers as directional cues to guide their migration toward group expansion.
“We wondered if you apply a force, and there's no friction, can the cells keep going fast without generating more force?” Pathak remarked. “We realized it's probably dependent on the environment. We thought they would be faster on aligned fibers, like railroad tracks, but what was surprising was that they were actually generating lower forces and still going faster.”
Amrit Bagchi, who earned a doctorate in mechanical engineering from McKelvey Engineering in 2022 in Pathak's lab and is now a postdoctoral researcher at the Center for Engineering MechanoBiology at the University of Pennsylvania, played a crucial role in the research setup. Bagchi created a soft hydrogel in the laboratory of Marcus Foston, associate professor of energy, environmental and chemical engineering, over several months during the COVID-19 pandemic. He then aligned the fibers using a special magnet at the School of Medicine before placing the cells on it to monitor their movement.
Bagchi developed a multi-layered motor-clutch model where the force-generating mechanisms in the cells act as the motor, and the clutch provides traction. This model was adapted for collective cells, incorporating three layers: one for cells, one for collagen fibers, and one for the custom gel beneath, allowing for intercommunication.
“Although the experimental results initially surprised us, they prompted the development of a theoretical model to explain the physics behind this counterintuitive behavior,” Bagchi stated. “Over time, we came to understand that cells use aligned fibers as a proxy for experiencing frictional forces in a manner that significantly differs from the random fiber condition. Our model's concept of matrix mechanosensing and transmission also predicts other known collective migration behaviors, such as haptotaxis and durotaxis, providing a unified framework for scientists to explore and potentially extend to other interesting cell migration phenotypes.”