The Extremely Low Mechanical Force Generated by Nano-Pulling Induces Global Changes in the Microtubule Network, Nuclear Morphology, and Chromatin Transcription in Neurons.

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