Spatiotemporal regulation of telomere motion by Lamin A/C in ATDC5 cells

Gene expression is regulated not only by biochemical cues but also by extracellular mechanical stimuli. Although the nuclear lamina is thought to mediate mechanical regulation of genome function, its role in controlling chromatin dynamics under changing mechanical environments remains unclear. In this study, we investigated how Lamin A/C regulates telomere motion by tracking fluorescently labeled telomeres in ATDC5 chondrogenic progenitor cells. Analysis across multiple substrate stiffness conditions (0.65, 3.5, 15, and 93 kPa) revealed modest region- and timescale-dependent changes in telomere motion, including a non-linear response in the nuclear interior. Lamin A/C depletion markedly enhanced the response of telomere motion to substrate stiffness in both the nuclear interior and periphery. Furthermore, Lamin A/C depletion altered nuclear morphology and chromatin organization. These results indicate that Lamin A/C constrains telomere motion and contributes to maintaining chromatin dynamics against extracellular mechanical perturbations. Our findings suggest that Lamin A/C may function as a mechanical buffer that suppresses stiffness-dependent changes in telomere motion.