Molecular resilience of neurons to repetitive mechanical compression.

Cells and organs constantly experience mechanical forces. Neurons, in particular, are exposed to such stimuli during development, aging, disease, and normal activities like movement and homeostasis. Recent studies highlight the key role of microtubules (MTs) in mechanotransduction, adjusting cytoskeletal dynamics in response to mechanical cues. While the effects of acute forces on MTs are known, the impact of repetitive mechanical stimuli over time remains unclear. In this study, we applied repetitive mechanical motion to neurons from the dorsal root ganglia and analyzed responses at varying strain levels. A 10% strain caused MT and organelle damage, leading to cell death. In contrast, a 2.5% strain did not harm cells and instead stabilized MTs. A 5% strain caused damage to the MT structure and leads to MT destabilization, but neurons activate a molecular response to counteract and recover from this damage, suggesting the involvement of the Ras pathway in response to injury. These findings suggest that neurons can adapt to repetitive mechanical stress, maintaining homeostasis when strain is below a certain threshold. Our results improve understanding of how mechanical forces influence neuronal structure and function, and how cells respond to injury by initiating protective pathways.