Figure 6. Simulating AR translocation with multimodal kinetics.

(a) Assuming three possible AR dynamical modes in the cytoplasm (diffusion, direct transport, and binding) based on literatures and our observations, we performed Monte-Carlo simulation of AR cytoplasm to nucleus translocation, specifically focusing on AR cytoplasm distribution over time and cytoplasm-nucleus concentration change. (b) A kymograph extracted from the same dataset as Fig. 1a, showing the AR distribution change in the cytoplasm after adding the agonist. From (c,e), we assigned a constant probability (nuclear permeability) of AR to be transported into the nucleus when it reaches the location of nuclear envelope. (c,d) Both diffusion only and direct transport only model showed the ability for AR to be transported to the nucleus within 30 minutes. Noticeably, with pure diffusion, the AR cytoplasm distribution is more close to the uniform distribution that was also observed in the actual measurement (see Fig. 1a,b,e), whereas in the case of pure transport, AR formed a sharp gradient in the cytoplasm, with the highest intensity happens at the nuclear envelope, and the space close to the cell membrane showed the absence of AR. (e) The mixture of diffusion, direct transport, and binding at different proportions alters the average time for AR translocation. However, the slope of change was preserved, in which a faster decline of AR cytoplasm concentration happened at the beginning. (f) Compared to the actual measurement shown in Fig. 1c,d, a model that considers linear increase of nuclear permeability represents more closely the observation, in which AR cytoplasm portion showed a slower decrease. See Method Simulation: AR multimodal translocation for simulation details and Supplementary Table 1 for the parameters used.