How cells sense and remember their environments

Amit Pathak received a $2.2 million NIH grant to explore how epithelial cells sense their environments and acquire mechanical memories

Shawn Ballard 03.03.2025

Detailed knowledge of how cells mechanically sense their environments is crucial to understanding processes like cancer and wound healing, where groups of cells might aggregate or migrate around stiff tissues and tumors. (iStock)

Facebook Twitter Linkedin Email

Mechanosensing is like a touchscreen on a smartphone. When you press on the screen, sensors detect the pressure and trigger a response, like opening an app. Similarly, cells sense mechanical forces in their environment and respond by activating molecular signaling and biological processes. This mechanical sensing enables necessary functions like growth and recovery.

Amit Pathak, professor of mechanical engineering & materials science in the McKelvey School of Engineering at Washington University in St. Louis, received a five-year, $2.2 million Maximizing Investigators' Research Award (MIRA) from the National Institutes of Health’s (NIH) National Institute of General Medical Sciences. The award supports Pathak’s work on how epithelial tissues, which line the gut, lungs and skin, sense and acquire memories of their environments over time. This project builds on his lab’s work in epithelial mechanobiology, launched in 2018 through the same funding mechanism.

The MIRA award allows scientists flexibility to adapt their research directions based on emerging results, which Pathak says will be especially helpful for his team to make new discoveries over the next five years.

"I'm excited to see what we can learn from systematically dissecting mechanosensing and memory,” Pathak said. “Cells ‘sense’ signals either at their surface or within their numerous skeletal components, including the nucleus. Their ‘mechanical memory’ comes from how they've previously responded to these signals. We’re curious about how millimeter-scale collective cell sheets sense micro-scale tissue injuries and remember repeated injuries, how cells optimize their forces and energy to move quickly through mechanically complex environments, and how the mechanics of individual nuclei can regulate large-scale collective cell behaviors."

By uncovering how epithelial cells mechanically sense and remember environmental stiffness, physical boundaries and disruptions in the extracellular matrix surrounding them, Pathak’s work has potential implications for new therapies for wound healing, cancer, fibrosis and developmental dysfunctions.

“Tissues vary in topography, confinement and fiber structure, which are sensed by different cellular components,” Pathak said. “By understanding which mechanical cues and cellular structures play the most significant roles in mechanosensing, we can identify more precise therapy targets for specific diseases. Our approach, which combines iterative mathematical modeling and experimentation, might also help us predict potential molecular targets for conditions like cancer and fibrosis, where tissue mechanics change alongside cellular mutations.”