Figure 3. Exploration strategies in the eukaryotic cell nucleus.
The TF exploration strategy can be determined by two numbers, the walk dimension dw and the diffusible space dimension df. (A) The MSD analysis of the diffusing molecules can be used to quantify dw, that is equal to 2 for Brownian diffusion and larger than 2 for hindered (anomalous) diffusion. (B) df describes the space that can be explored by the TF, and it is equal to 1, for molecules sliding on DNA, 2 for molecules exploring surfaces, 3 for molecules diffusing freely in 3D. If the diffusible space is obstructed on multiple scales, df can be smaller than 3. (C) When dw > df, the exploration is compact and the TF visits all the sites of a region of space before leaving it. Oppositely, when dw > df the exploration is non-compact and the TF samples the potential targets only sparsely. Compact and non-compact exploration can be combined together intermittently, and this combination can guide the TF molecules to their target sites speeding up the search process. (D) The anisotropy of the diffusion process (measured as the distribution of angles between consecutive displacements) can inform on the search strategy, as compact exploration should result in high backward anisotropy. (E) Measuring the diffusional anisotropy as function of the distance jumped by the molecules can reveal exploration modes, including the presence of trapping zones that underlie guided exploration.