Cyclic-polymer grafted colloids in spherical confinement: insights for interphase chromosome organization

Abstract

Interphase chromosome structures are known to remain segregated in the micron-sized eukaryotic cell nucleus and occupy a certain fraction of nuclear volume, often without mixing. Using extensive coarse-grained simulations, we model such chromosome structures as colloidal particles whose surfaces are grafted by cyclic polymers. This model system is known as Rosetta. The cyclic polymers, with varying polymerization degrees, mimic the functionality of structural protein complexes, while the rigid core models the chromocenter sections of chromosomes. Our simulations show that the colloidal chromosome model provides a well-segregated particle distribution without specific attraction between the chain monomers. Notably, linear-polymer grafted particles also provide the same segregation scheme. However, unlike linear chains, cyclic chains result in less contact between the polymer layers of neighboring chromosome particles, demonstrating the effect of DNA breaks in altering genome-wide contacts. As the polymerization degree of the chains decreases while maintaining the total chromosomal length (the total polymer length per particle), particles form quasi-crystalline order, reminiscent of a glassy state. This order weakens for polymer chains with a characteristic size on the order of the confinement radius. Our simulations demonstrate that polymer systems can help decipher 3D chromosomal architectures along with fractal globular and loop-extrusion models.