Structural and functional axonal plasticity following mechanical stimulation

Organs and cells of our body are constantly subjected to mechanical forces. Neurons experience mechanical stimuli during neurodevelopment, aging, pathologic conditions and in everyday functions such as homeostatic processes and movement. Recent literature highlights microtubules (MTs) as crucial mediators in mechanotransduction. While the effects of transient and acute forces on neurons have been explored, the impact of repetitive mechanical stresses throughout the lifespan remain mostly unknown. Recently, in vitro studies have unveiled that repetitive mechanical motion can damage MTs. How do cells, which are subjected to mechanical stress daily, withstand this stimulation and keep working throughout our long lives? Using a device that applies compressive strains, I simulated the mechanical stress neurons experience daily. My findings show that mechanical stress intensity is key to neuronal fate. I found that low stress (2.5%) activates protective mechanisms, such as increased MT acetylation, preserving axon integrity. Moderate stress (5%) temporarily disrupts MT organization and reduces axon length, but neurons gradually recover structure and function, likely through repair mechanisms. However, high stress (10%) induces irreversible damage and cell death, revealing a critical threshold beyond which repair fails. These findings provide new insights into neuronal resilience and lay the groundwork for identifying how cellular functions can be restored.