Chromatin compaction states, nuclear shape fluctuations and auxeticity: A biophysical interpretation of the epigenetic landscape of stem cells

When embryonic stem cells differentiate, the mechanical properties of their nuclei evolve en route to their terminal state. Measurements of the deformability of cell nuclei in the transitional state that intervenes between the embryonic stem cell state and the differentiation primed state of mouse stem cells, indicate that such nuclei are auxetic i.e. have a negative Poissons ratio. We show, using a theoretical model, how this unusual mechanical behaviour results from the coupling between chromatin compaction states and nuclear shape. Our biophysical approach, which treats chromatin as an active polymer system whose mechanics is modulated by nucleosome binding and unbinding, reproduces experimental results while providing new predictions. We discuss ways of testing these predictions. Our model suggests a biophysical interpretation of the epigenetic landscape of stem cells.