Chromatin viscoelasticity measured by local dynamics analysis

  Anat Vivante  ,  Irena Bronshtein  ,  Yuval Garini  
Physics Department and Nanotechnology Institute, Bar Ilan University, Ramat Gan, Israel

The nucleus in eukaryotic cells is a crowded environment that consists of genetic code along the DNA, together with a condensed solution of proteins, RNA, and other molecules. It is subjected to highly dynamic processes including cell division, transcription, DNA repair, and others. In addition, the genome in the nucleus is subjected to external forces applied by the cytoplasmic skeleton and neighboring cells as well as by internal nuclear forces. These forces oppose the need to maintain the genome order, that may be compensated by the internal nuclear viscoelastic properties that can restrain these forces.

The structural and mechanical properties of chromatin inside the nucleus are still not fully clear; however, their importance for the proper function of the cells is unquestionable. Different approaches have been developed for this aim, ranging from direct measurement of the dynamic and elastic properties of chromatin, to studies of the interactions of chromatin with the surrounding envelope and nuclear bodies. Although the elasticity of naked DNA in vitro is well characterized, the elasticity of chromatin in live cells is more complex and still not fully understood.

Here we studied the elastic properties of chromatin by dynamic measurements in live cells, followed by viscoelastic modeling. We measured the trajectories of single chromatin loci, centromeres, and telomeres in live cells and analyzed their dynamics using the Langevin formalism. We assumed that the overall effect of the chromatin network forces can be modeled for each locus by a local harmonic potential and calculated the effective force constant. We assumed that this harmonic force results from the chromatin network formed by the internal polymer structure together with cross-links formed by the protein complex. We show that lamin A has the highest effect on chromatin viscoelasticity and its removal leads to a significant reduction in the local harmonic force.