Chromatin
is a DNA–protein complex that is densely packed
in the cell nucleus. The nanoscale chromatin compaction plays critical
roles in the modulation of cell nuclear processes. However, little
is known about the spatiotemporal dynamics of chromatin compaction
states because it remains difficult to quantitatively measure the
chromatin compaction level in live cells. Here, we demonstrate a strategy,
referenced as DYNAMICS imaging, for mapping chromatin organization
in live cell nuclei by analyzing the dynamic scattering signal of
molecular fluctuations. Highly sensitive optical interference microscopy,
coherent brightfield (COBRI) microscopy, is implemented to detect
the linear scattering of unlabeled chromatin at a high speed. A theoretical
model is established to determine the local chromatin density from
the statistical fluctuation of the measured scattering signal. DYNAMICS
imaging allows us to reconstruct a speckle-free nucleus map that is
highly correlated to the fluorescence chromatin image. Moreover, together
with calibration based on nanoparticle colloids, we show that the
DYNAMICS signal is sensitive to the chromatin compaction level at
the nanoscale. We confirm the effectiveness of DYNAMICS imaging in
detecting the condensation and decondensation of chromatin induced
by chemical drug treatments. Importantly, the stable scattering signal
supports a continuous observation of the chromatin condensation and
decondensation processes for more than 1 h. Using this technique,
we detect transient and nanoscopic chromatin condensation events occurring
on a time scale of a few seconds. Label-free DYNAMICS imaging offers
the opportunity to investigate chromatin conformational dynamics and
to explore their significance in various gene activities.