Mixing and segregation of ring polymers: spatial confinement and molecular crowding effects

Abstract

During the life cycle of bacterial cells the non-mixing of the two ring-shaped daughter genomes is an important prerequisite for the cell division process. Mimicking the environments inside highly crowded biological cells, we study the dynamics and statistical behavior of two flexible ring polymers in the presence of cylindrical confinement and crowding molecules. From extensive computer simulations we determine the degree of ring-ring overlap and the number of inter-monomer contacts for varying volume fractions ϕ of crowders. We also examine the entropic demixing of polymer rings in the presence of mobile crowders and determine the characteristic times of the internal polymer dynamics. Effects of the ring length on ring-ring overlap are also analyzed. In particular, on systematic variation of the fraction of crowding molecules, a ϕ − ( ) 1 -scaling is found for the ring-ring overlap length along the cylinder axis, and a non-monotonic dependence of the 3D ring-ring contact number with a maximum at ϕ ≈ 0.2 is obtained. Our results demonstrate that polymer rings are demixed and separated by particular entropy-favourable partitioning of crowders along the axis of the cylindrical simulation box. These findings help to rationalize the implications of macromolecular crowding for circular DNA molecules in confined spaces inside bacteria as well as in localized cellular compartments inside eukaryotic cells. 2 0 . 5 9 in terms of the ring New J. Phys. 16 (2014) 053047 J Shin et al New J. Phys. 16 (2014) 053047 J Shin et al R 2 0.9 was predicted [44, 77]. New J. Phys. 16 (2014) 053047 J Shin et al 6 From the corresponding probability density Δ ( ) p z AB CM along the cylinder axis we compute the free energy of the overlap of the two rings in terms of New J. Phys. 16 (2014) 053047 J Shin et al 7 New J. Phys. 16 (2014) 053047 J Shin et al 8 New J. Phys. 16 (2014) 053047 J Shin et al AB and N n AB . These results are illustrated in figure 13, which is New J. Phys. 16 (2014) 053047 J Shin et al 15 New J. Phys. 16 (2014) 053047 J Shin et al 16 4 Recent experiments show that in E. coli active protein oscillations guide the demixing of the chromosomes and thus assist entropic effects, see [83].

Universal scaling of crowding-induced DNA mobility is coupled with topology-dependent molecular compaction and elongation

“…Such similarity is surprising given the large differences reported between the mobility of ring and linear polymers (including DNA) in entangled and complex crowded environments. 33,38 However, in these studies the size of crowders and tracked polymers are more comparable to each other than in our experiments where the R G of dextran is 4100Â smaller than that of DNA. 2, inset), as we previously reported for crowded linear DNA of varying lengths.…”

“…33 Thus, these important questions have remained unanswered. These findings raise the question: is there a similar mechanism that rings can access to facilitate mobility in the cell?…”

How are molecular crowding and the spatial organization of a biopolymer interrelated

“…The applicability of such a model can be tested in terms of the extent to which it serves its purpose. Indeed, similar coarsegrained models have been useful for gaining quantitative insights into a large-scale behavior of biomolecular systems (e.g., chromosome organization and segregation) 17,[23][24][25]30,32 . On the other hand, the small-a case is relevant for protein or RNA folding [2][3][4]8 .…”

Molecular simulations of cellular processes

“…These simulations indicate that a balance between flexibility and confinement is necessary to allow chromosomal segregation and correct loci positioning. Macromolecular crowders, absent in this model, have also been found to contribute to segregation of the genetic material (Shin et al 2014).…”