Mechanosensing functions similarly to a touchscreen on a mobile device. When you press the display, sensors recognize the pressure and initiate a reaction, such as launching an application. In the same vein, cells perceive mechanical forces within their surroundings and react by activating molecular signaling and biological activities. This mechanical perception facilitates essential operations like growth and healing.

Amit Pathak, a faculty member in mechanical engineering and materials science at the McKelvey School of Engineering at Washington University in St. Louis, has been awarded 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. This funding supports Pathak’s exploration of how epithelial tissues, which line the gut, lungs, and skin, detect and retain memories of their surroundings over time.

This initiative builds upon his laboratory’s research in epithelial mechanobiology, initiated in 2018 with the same funding source.

The MIRA grant provides scientists the adaptability to modify their research paths based on new findings, which Pathak believes will be particularly beneficial for his team in making novel discoveries over the next five years.

“I’m thrilled to discover what insights we can gain from methodically exploring mechanosensing and memory,” Pathak expressed. “Cells ‘detect’ signals either at their exterior or throughout their various structural elements, including the nucleus. Their ‘mechanical memory’ derives from their past reactions to these signals. We’re intrigued by how millimeter-scale collective cell layers perceive micro-scale tissue injuries and retain memories of repeated injuries, how cells optimize their forces and energy for swift movement through mechanically intricate environments, and how the mechanics of individual nuclei might govern large-scale collective cell activities.”

By elucidating how epithelial cells mechanically perceive and remember environmental stiffness, physical boundaries, and disruptions within the extracellular matrix that encases them, Pathak’s research offers promising implications for innovative treatments in wound repair, cancer, fibrosis, and developmental disorders.

“Tissues differ in topography, confinement, and fiber composition, which are acknowledged by various cellular components,” Pathak noted. “By deciphering which mechanical indicators and cellular frameworks play critical roles in mechanosensing, we can pinpoint more exact therapeutic targets for particular illnesses.”

“Our methodology, which merges iterative mathematical modeling with experimentation, could also assist us in forecasting potential molecular targets for ailments like cancer and fibrosis, wherein tissue mechanics evolve alongside cellular mutations.”

This article was originally published on the McKelvey Engineering website.

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