Transient Anomalous Diffusion of Telomeres in the Nucleus of Mammalian Cells

We measured individual trajectories of fluorescently labeled telomeres in the nucleus of eukaryotic cells in the time range of ${10}^{-2}–{10}^4\sec $ by combining a few acquisition methods. At short times the motion is subdiffusive with $⟨r^2⟩\sim t^{\alpha }$ and it changes to normal diffusion at longer times. The short times diffusion may be explained by the reptation model and the transient diffusion is consistent with a model of telomeres that are subject to a local binding mechanism with a wide but finite distribution of waiting times. These findings have important biological implications with respect to the genome organization in the nucleus.

Figure 1

(A) Projection image of a 3D data. Typical distribution of telomeres (bright spots) in the nucleus stained with 4’-6-diamidino-2-phenylindole dihydrochloride (DAPI). (B) 3D motion of a telomere (bright object) as measured over $2\times {10}^3$ sec. (C) 2D motion of a telomere in 18 sec measured at 5 Hz. A fixed telomere from a dead cell is also shown (shifted upwards) indicating that the measurement precision is better than 15 nm. (D) $X$, $Y$ motion of a telomere during 20 seconds measured with the confocal setup.

Figure 2

Log-log plot of $⟨r^2⟩/t$ vs $t$. The average MSD is shown in black. The standard deviation is also shown. The data were analyzed in three time ranges (Table ). The analysis after drift and rotation correction is performed only on 2D data. The diffusion is anomalous up to $\sim 100\sec$ where it changes to normal diffusion.

Figure 3

The MSD of single telomeres on a log-log scale in the anomalous time range of ${10}^{-2}–{10}^2$ sec. The thick line shows the average MSD shifted upward for clarity.