Chromosome dynamics, molecular crowding, and diffusion in the interphase cell nucleus: a Monte Carlo lattice simulation study

Abstract

Using Monte Carlo simulations, we have investigated the decondensation of chromosomes during interphase and the diffusive transport of spherical probe particles in the chromatin network. The chromatin fibers are modeled as semiflexible polymer chains on a fixed three-dimensional grid, taking into account their flexibility and eventual chain crossing by the aid of topoisomerases. The network thus created will obstruct the diffusion of macromolecules. A result of our simulations is that crowding of diffusing molecules leaves the dynamics of the chromosomes and the behavior of other diffusing molecules qualitatively unaffected. Furthermore, the capability of the simulated chromatin network to trap diffusing molecules over long times is lower than that measured in microrheological experiments. Microrheology is a technique that allows to determine the viscoelastic properties of a material by the motion of embedded tracer particles. Long-time trapping requires a stiff network, as only such a network quickly responds to the diffusive fluctuations of tracers and prevents them from squeezing through meshes. A high degree of crosslinking amplifies this effect. The presence of a flexible and uncrosslinked polymer simply increases the effective viscosity sensed by tracer particles. The diffusion of tracers in our simulations reveals rather viscous than elastic chromatin networks, suggesting that chromatin alone cannot account for the high elasticity of the cell nucleus.