Figure 4. Mechanical competition (tug of war) between processive zippering and active telomere forces.

(A). Simulation of tug of war. Two chromosomes, represented as beads connected by springs, are initialized into a state where half the nodes are paired (indicated by dots) and the other half is unpaired. The unpaired region is then allowed to relax under influence of Langevin random forces. Next, active forces are applied at the unpaired telomeres, and the simulation is run with this constant force applied in a uniform direction. As illustrated on the right, two possible outcomes are that either the telomere force is able to pull the chromosomes apart, leading to unzippering, or else the zippering can overcome the telomere pulling and drive further pairing beyond the initial extent of pairing. (B) Pairing kymographs showing results for three different magnitudes of telomere force. Each kymograph is made by plotting the pairing status of all loci on the chromosome as a vertical color bar, in which color reflects distance between homologous loci, with blue indicating fully paired and red fully unpaired. These color bars for each timepoint are then stacked side by side from left to right showing progressing of pairing over time. Black bars under each kymograph indicate the initial 2000 timepoints during which the unpaired region is allowed to stretch while the initial paired region is locked in the paired state. During these simulations, the telomere forces are applied in constant, opposite directions at the two telomeres. It is important to note that unlike previous simulations, the telomere force is applied in a constant direction, and does not fluctuate. All kymographs in this figure were generated using an unpairing rate constant of 0.01, with the different forces applied at the telomeres as indicated. All simulations for this figure were performed using a nuclear radius of 50.