Following the Dynamics of DNA in Living Cells

Cells are brimming with molecular activity, but the cellular interior is much more than a test tube for biochemical reactions. The intracellular environment imposes a variety of mechanical constraints and engenders interactions from molecular crowding to a range of motor-driven activity responsible for transcription, replication, cargo transport, cytoskeletal rearrangement, chromosomal remodeling, and so on. We have developed a two-color correlational microscopy technique to follow the dynamics of DNA interacting with the \textit{in vivo} cellular environment. Substantial differences between live cells and dead, yet structurally intact, cells point to a strong coupling of active, motor-driven fluctuations in the cell. This suggests that the motion of native, cellular DNA may similarly be driven by active processes, instead of relying on purely thermal, passive fluctuations. We also note that the correlations provide a sensitive measure for the effective length of the DNA probe on a length scale around one persistence length ($\sim $ 50 nm). This paves the way for experiments with more complex DNA probes that can bind transcription factors to form protein-mediated DNA loops, the dynamics of which could be observed through this method.