Coarse-Grained model of the demixing of DNA and non-binding globular macromolecules

TL;DR

This study presents a coarse-grained model demonstrating that DNA compaction in prokaryotic cells results from demixing driven by crowding effects and crowder size, supporting the demixing hypothesis for nucleoid formation.

Contribution

It introduces a new coarse-grained model analyzing DNA and crowder demixing, highlighting the role of crowding and crowder size in nucleoid formation.

Findings

DNA compaction is governed by crowder volume occupancy ratio.

Strong compaction occurs near jamming density, indicating synergistic crowding and electrostatic effects.

Larger crowders preferentially demix with DNA, supporting the demixing mechanism.

Abstract

The volume occupied by the unconstrained genomic DNA of prokaryotes in saline solutions is thousand times larger than the cell. Moreover, it is not separated from the rest of the cell by a membrane. Nevertheless, it occupies only a small fraction of the cell called the nucleoid. The mechanisms leading to such compaction are the matter of ongoing debates. The present work aims at exploring a newly proposed mechanism, according to which the formation of the nucleoid would result from the demixing of the DNA and non-binding globular macromolecules of the cytoplasm, like ribosomes. To this end, a coarse-grained model of prokaryotic cells was developed and demixing was analyzed as a function of the size and number of crowders. The model suggests that compaction of the DNA is actually governed by the volume occupancy ratio of the crowders and remains weak almost up to the jamming critical density. Strong compaction is however observed just before jamming, suggesting that crowding and electrostatic repulsion work synergetically in this limit. Finally, simulations performed with crowders with different sizes indicate that the DNA and the largest crowders demix preferentially. Together with the recent observation of the gradual compaction of long DNA molecules upon increase of the concentration of BSA proteins and silica nanoparticles, this work supports the demixing mechanism as a key player for the formation of the nucleoid.