Chromatin Rheology Tells a Story: From DNA Damage Loci to Cellular Monolayers*

Over the past two decades here have been numerous intellectual intersections between polymer physics and modeling of intracellular environments including (i) soft glassy rheology as a description of the numerous relaxation states within the cell and (ii) athermal rheology from the contribution of cellular molecular motors. Within the nucleus we have also observed a powerlaw response of chromatin both by extracellular applied force and by particle tracking microrheology. Global condensation state of the chromatin greatly impacts its rheology, and both can be manipulated with epigenetic modifying drugs (trichostatin A) or growth factors. Locally, chromatin condensation can be manipulated with other methods such as tetracycline responsive elements (TRE) or is altered during transcription. We have developed methods to image changes in these regions using fluorescence lifetime imaging and particle tracking combined with multichannel registration and processing to determine the effects of DNA damage on heterochromatin and euchromatin. Measuring the impact of molecular motors within the cell show that actin-myosin forces produced in the cytoskeleton are transmitted into the nucleus where the athermal motions can be registered by nuclear particle tracking, thus allowing the dense chromatin to be used as a sensor for cellular force generation. This technique, which we refer to as SINK (Sensors from IntraNuclear Kinetics) has allowed us to determine strain variations within heterogeneous monolayers of cells. Mechanical defects in cell monolayers shows exponential propagation, which suggests that monolayers of cells may be better modeled as colloidal crystals than continuum sheets. The study of condensed chromatin inside of cells has provided interesting physical and biological insights into cells at length scales of tens of nanometers to hundreds of micrometers.