Universal Aspects of Chromosome Folding

During cell division (mitosis) chromosomes adopt a compact form that is suitable for transport. During periods of normal cell activity (interphase), they decondense inside the cell nucleus. Being long-chain molecules (in the case of human chromosomes the contour length of the chromatin fiber is on the order of 1 mm), the random thermal motion of interphase chromatin fibers is hindered by entanglements, similar to those restricting the manipulation of a knotted ball of wool. In the first part of the talk, I will show that entanglement effects cause sufficiently long chromosomes to remain segregated during interphase and to form “territories.” In particular, our model reproduces with zero adjustable parameters currently avaliable experimental results for the internal chromosome structure and dynamics in interphase nuclei as measured in Fluorescence in-situ hybridization (FISH) and chromosome conformation capture (3C, HiC) experiments. In the second part of the talk, I will explore the subtle physics of solutions of non-concatenated ring polymers as a model for interphase nuclei. We develop a multi-scale approach combining massive Molecular Dynamics simulations on the fiber level with Monte Carlo simulations of a lattice model of interacting, randomly branched polymers for the fractal, large scale crumpled loop structure. We show that not only the territorial confinement but also other characteristic features of chromosome folding such as the loop-on-loop structure of internal contacts arise as a generic consequence of the polymeric nature of chromosomes.