Heterogeneous force response of chromatin in isolated nuclei

A quantitative description of nuclear mechanics is crucial for understanding its role in force sensing within eukaryotic cells. Recent studies indicate that the chromatin within the nucleus cannot be treated as a homogeneous material. To elucidate its material properties, we combine optical tweezers manipulation of isolated nuclei with multi-color fluorescence imaging of lamin and chromatin to map the response of nuclei to local deformations. Force spectroscopy reveals nuclear strain stiffening and an exponential force dependence, well described by a hierarchical chain model. Simultaneously, fluorescence data show a higher compliance of chromatin compared to the nuclear envelope at strains