Subdiffusive Dynamics of Optogenetic Droplets Report on Local Chromatin Mechanics

DNA is organized into chromatin, a complex material which stores information and controls gene expression. Liquid-liquid phase separation is believed to be a principal mechanism governing its organization. Previous work with optogenetically activatable droplets demonstrated that liquid condensates displace chromatin. Here, we show that droplet growth dynamics are directly inhibited by chromatin. Generally, droplet radii follow a power law scaling with time, such that R~t^β. We observe an anomalously slow coarsening exponent during interphase but recover dynamics more consistent with classical theory when chromatin is condensed during mitosis. We show that this slowed growth is due to subdiffusion of individual condensates, a clear signature of elastic behavior in the nucleus. We further apply this framework to elucidate local mesoscopic mechanics of the nucleus in various biologically relevant contexts. Thus, our work demonstrates the use of engineered intracellular condensates as “probes” of local mesoscale nuclear organization.