Mechanical Interplay of Chromatin and Liquid-Liquid Phase Separated Condensates*

DNA is organized into chromatin, a complex material which stores information and controls gene expression. One mechanism for biological organization, particularly in the crowded nucleus, is liquid-liquid phase separation (LLPS). Here, we use two optogenetic technologies to show that liquid condensates displace chromatin as they grow. We also demonstrate that these synthetic condensates localize to regions of low-density chromatin. We develop a minimal physical model to explain this stiffness selectivity, wherein droplets prefer low-density chromatin regions due to a lower mechanical energy of deformation. By utilizing these spatiotemporally-controllable optogenetic systems, we construct a phase diagram of an intrinsically disordered transcriptional regulator and estimate the stiffness of the chromatin network. Our work thus not only sheds light on the role of LLPS in chromatin organization but also uses the physical principles of phase separation to elucidate mesoscale features of the nucleus.