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

Abstract

In a crowded cellular interior, dissolved biomolecules or crowders exert excluded volume effects on other biomolecules, which in turn control various processes including protein aggregation and chromosome organization. As a result of these effects, a long chain molecule can be phaseseparated into a condensed state, redistributing the surrounding crowders. Using computer simulations and a theoretical approach, we study the interrelationship between molecular crowding and chain organization. In a parameter space of biological relevance, the distributions of monomers and crowders follow a simple relationship: the sum of their volume fractions rescaled by their size remains constant. Beyond a physical picture of molecular crowding it offers, this finding explains a few key features of what has been known about chromosome organization in an E. coli cell.

A segregative phase separation scenario of the formation of the bacterial nucleoid

“…The crucial point is that simulations performed with this latter model led to rather different results, depending on whether the size of crowders was assumed to be smaller (the "bacterial chromosome limit") or larger (the "protein folding limit") than the size of the connected beads. [45,46] It can consequently be expected that the results obtained with the present model will, somewhat paradoxically, be closer to those pertaining to the "protein folding limit" of Refs. [45,46] rather than the "bacterial chromosome limit".…”

“…The models used in this study share several common points with those developed previously to investigate facilitated diffusion, [52][53][54] the interactions of H-NS proteins and DNA, [55][56][57], the formation of the bacterial nucleoid, [4,5,48,[44][45][46][47] as well as questions dealing with spatial confinement and molecular crowding, [58,59] More precisely, genomic DNA is represented by a circular chain of 1440 n = beads of radius a separated at equilibrium by a distance 0 5.0 l = nm, where each bead represents 15 consecutive base pairs. The DNA chain is enclosed in a confining sphere of radius 0 120 R = nm (see Fig.…”

“…In contrast, in Refs. [44][45][46][47] [44][45][46][47]. The crucial point is that simulations performed with this latter model led to rather different results, depending on whether the size of crowders was assumed to be smaller (the "bacterial chromosome limit") or larger (the "protein folding limit") than the size of the connected beads.…”

“…[48] As anticipated in the Simulation Models and Methods section, it is interesting to note that this result is indeed closer to the "protein folding limit" of Refs. [45,46], for which compaction was also shown to be governed by the volume fraction of the crowders, rather than the "bacterial chromosome limit", for which it is the ratio of the volume fraction and the size of the crowders that matters. [45,46] It is nonetheless emphasized that the size of the DNA coil evolves much more smoothly and gradually with the volume fraction of the crowders for the "protein folding limit" of Refs.…”

“…[45,46], for which compaction was also shown to be governed by the volume fraction of the crowders, rather than the "bacterial chromosome limit", for which it is the ratio of the volume fraction and the size of the crowders that matters. [45,46] It is nonetheless emphasized that the size of the DNA coil evolves much more smoothly and gradually with the volume fraction of the crowders for the "protein folding limit" of Refs. [45,46] than for the present model, a difference which is probably ascribable to the bending rigidity, which in the present model opposes compaction efficiently up to the jamming threshold, where intermolecular interactions finally become predominant.…”