How Do Cells Respond to Exercise and Physical Activity?
Researchers have uncovered a novel mechanism that dictates how cells respond to exercise.
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Scientists at the Perron Institute for Neurological and Translational Science and The University of Western Australia have made a significant breakthrough in understanding how cells in our body respond to physical activity and exercise. They’ve discovered a direct mechanical signal that travels from outside the cell into the energy-producing parts of the cell, which could change the way we think about exercise and its benefits.
The international study, led by Dr Ziming Chen and Professor Minghao Zheng was published in Science Advances overnight (26 June). The researchers found that a protein production factory in the cell, called the endoplasmic reticulum (ER), can sense external mechanical forces, such as stretching or strain, and transmit them deep into the cell. This process helps regulate energy production in the cell and maintains tissue health.
“Cells constantly experience physical forces, especially in load-bearing tissues such as tendon, muscle, and lung,” said Dr Ziming Chen, Postdoctoral scientist at UWA School of Biomedical Sciences and the first author of the paper. “We found that the ER plays a central role in converting these mechanical cues into metabolic responses, controlling how cells produce energy and prevent tissue damage.”
The team used custom-designed bioreactors and a suite of advanced genetic and microscopy techniques to study the effects of mechanical strain on cells. They discovered that while moderate physical activity and exercise can enhance energy production in cells, excessive strain or injury can disrupt this process, leading to cellular damage. They identified a “sweet spot” of mechanical loading that can boost energy production and promote cellular health.
Professor Zheng, leader of the research team at UWA and Perron Institute and senior corresponding author of the paper said “This research has significant implications for understanding how our tendons and ligaments respond to exercise and physical activity.”
“This discovery could lead to a better understanding of how to prevent injuries and improve tissue health, opening the door for new treatments that mimic the benefits of exercise, particularly for patients with neurodegenerative conditions, such as motor neurone disease, who are unable to engage in physical activity. It could also have broader implications for various conditions including tendinopathy, osteoporosis, hypertension and asthma.”
Reference: Chen Z, Chen P, Li J, et al. External strain on the plasma membrane is relayed to the endoplasmic reticulum by membrane contact sites and alters cellular energetics. Sci Adv. 2025;11(26):eads6132. doi: 10.1126/sciadv.ads6132
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