Abstract
The nucleus in eukaryotic cells is the site for genomic functions such as RNA transcription, DNA replication, and DNA repair/recombination. However, the nucleus is subjected to various mechanical forces associated with diverse cellular activities, including contraction, migration, and adhesion. Although it has long been assumed that the lamina structure, underlying filamentous mesh-work of the nuclear envelope, plays an important role in resisting mechanical forces, the involvement of compact chromatin in mechanical resistance has also recently been suggested. However, it is still unclear how chromatin functions to cope with the stresses. To address this issue, we studied the mechanical responses of human cell nuclei by combining a force measurement microscopy setup with controlled biochemical manipulation of chromatin. We found that nuclei with condensed chromatin possess significant elastic rigidity, whereas the nuclei with a decondensed chromatin are considerably soft. Further analyses revealed that the linker DNA and nucleosome-nucleosome interactions via histone tails in the chromatin act together to generate a spring-like restoring force that resists nuclear deformation. The elastic restoring force is likely to be generated by condensed chromatin domains, consisting of interdigitated or "melted" 10-nm nucleosome fibers. Together with other recent studies, it is suggested that chromatin functions not only as a "memory device" to store, replicate, and express the genetic information for various cellular functions but also as a "nuclear spring" to resist and respond to mechanical forces.