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<p>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.</p><p></p>

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Molecular resilience of neurons to repetitive mechanical compression

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月17日

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  • Allegra Coppini,
  • Valentina Cappello,
  • Syeda Rubaiya Nasrin,
  • Alessandro Falconieri,
  • Oz Mualem,
  • Gadiel Saper,
  • Orit Shefi,
  • Henry Hess,
  • Akira Kakugo,
  • Vittoria Raffa

摘要

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.