Periodic confined cell migration drives partially reversible chromatin reorganization in cancer cell lines

Cells throughout physiological and pathological contexts are exposed to a broad spectrum of mechanical stimuli, triggering extensive nuclear deformation and chromatin remodeling. These mechanical cues drive the cell to dynamically adapt through coordinated structural, epigenetic, and biochemical mechanisms to withstand mechanical stress while protecting genomic integrity. However, whether such cellular adaptations are reversible or result in persistent alterations remains unresolved. In cancer metastasis, addressing this issue is critical: confined migration through narrow pores prompts chromatin condensation with heterochromatin enrichment, yet cancer cells must preserve their oncogenic potential while preparing for future deformations. Therefore, the ability of these cells to reconcile reversible chromatin remodeling and mechanical memory could be key to metastatic resilience. Here, using a custom-designed microfluidic device to monitor single-cell chromatin reorganization, we show confined migration induces partially-reversible chromatin condensation: total highly-condensed chromatin content is recovered after deformation, but the distribution of condensed chromatin clusters remains altered. Our findings highlight this duality of chromatin condensation as both a short-term adaptive response and a mechanical memory strategy, which could potentially contribute to address cancer invasiveness.