The extremely low mechanical force generated by nano-pulling induces global changes in the microtubule network, nuclear morphology, and chromatin transcription in neurons

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Mechanical force plays a pivotal role in every aspect of axon development. In this paper, we explore the use of nano-pulling, a technology that enables the intracellular generation of extremely low mechanical forces. We demonstrate that force-mediated axon growth also exerts global effects that extend to the nuclear level. Our mechanistic studies support a model in which exogenous forces induce stabilization of microtubules, and a significant remodeling of perinuclear microtubules, which preferentially align perpendicularly to the nuclear envelope. We observed an increase in the lateral tension of the nucleus, leading to substantial remodelling of nuclear morphology, characterized by an increase in nuclear grooves and higher sphericity index (indicating less flattened nuclei). Notably, these changes in nuclear shape are linked to chromatin remodelling, resulting in global transcriptional activation.