| Autor: |
Forman J; School of Biomedical Engineering, Colorado State University, Fort Collins, CO, USA.; Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO, USA.; Translational Medicine Institute, Colorado State University, Fort Collins, CO, USA., Hine B; School of Biomedical Engineering, Colorado State University, Fort Collins, CO, USA.; Translational Medicine Institute, Colorado State University, Fort Collins, CO, USA.; Department of Mechanical Engineering, Colorado State University, Fort Collins, CO, USA., Kaonis S; School of Biomedical Engineering, Colorado State University, Fort Collins, CO, USA.; Translational Medicine Institute, Colorado State University, Fort Collins, CO, USA., Ghosh S; School of Biomedical Engineering, Colorado State University, Fort Collins, CO, USA.; Translational Medicine Institute, Colorado State University, Fort Collins, CO, USA.; Department of Mechanical Engineering, Colorado State University, Fort Collins, CO, USA.; Cell and Molecular Biology, Colorado State University, Fort Collins, CO, USA. |
| Abstrakt: |
Cell migration involves the actin cytoskeleton, and recently recognized nuclear involvement. In this study, we explore the impact of chromatin remodeling on cell migration using NIH 3T3 cells and a scratch wound assay subjected to pharmacological interventions. We inhibit histone deacetylases (HDACs) with Trichostatin A (TSA) and methyltransferase EZH2 with GSK126 to modulate chromatin compaction. Our results indicate that chromatin modifications impair wound closure efficiency, reduce individual cell migration speed, and disrupt migration persistence. Live-cell imaging reveals dynamic intranuclear chromatin remodeling and nuclear shape parameters during migration, influenced by both small- and large-scale chromatin remodeling. The altered nuclear shape is associated with disrupted cell and nuclear mechanics, suggesting a crucial interplay between chromatin remodeling, nuclear mechanics and migration. These findings shed light on the intricate connection between intranuclear chromatin dynamics, nuclear mechanics, and cell migration, providing a basis for further investigations into the molecular mechanisms governing these processes. |
