Quantifying Nanoscale Viscosity and Structures of Living Cells Nucleus from Mobility Measurements

Understanding
the mobility of nano-objects in the eukaryotic cell
nucleus, at multiple length-scales, is essential for dissecting nuclear
structure–function relationships both in space and in time.
Here, we demonstrate, using single-molecule fluorescent correlation
spectroscopies, that motion of inert probes (proteins, polymers, or
nanoparticles) with diameters ranging from 2.6 to 150 nm is mostly
unobstructed in a nucleus. Supported by the analysis of electron tomography
images, these results advocate the ∼150 nm-wide interchromosomal
channels filled with the aqueous diluted protein solution. The nucleus
is percolated by these channels to allow various cargos to migrate
freely at the nanoscale. We determined the volume of interchromosomal
channels in the HeLa cell nucleus to 237 ± 61 fL, which constitutes
34% of the cell nucleus volume. The volume fraction of mobile proteins
in channels equals 16% ± 4%, and the concentration is 1 mM.