Self-Organized Protein Localization and DNA Segregation Inside Bacterial Cells

Abstract

Asymmetric cell division in C.Crescentus relies on differentially localizing certain proteins to the poles where they bind to the scaffolding protein PopZ that displays a bipolar pattern. On the other hand, expressing PopZ in E. coli favours unipolar patterning. Additionally, the aggregation of misfolded proteins as well as plasmids in bacteria also display unipolar and biopolar patterns, similar to that of PopZ. These different systems have led to the hypothesis that chromosome free regions + biomolecular aggregation can be sufficient to drive localization in bacterial cells. We have performed Monte-Carlo simulations to show that the entropic force provided by the self-avoiding chromosome confined in the cylindrical geometry of the cell and the energy gained from aggregation results in phase separation between proteins and the polymer. We fully explore the phase space showing how patterning depends on protein concentration, chromosome density, cell shape and aggregation strength. The exploration results in a rich phase diagram of patterns which the observed systems can be fit into. Additionally, the dynamics of pattern formation depends somewhat on the rate at which proteins are added to the system. When proteins are added very slowly to the cell, the unipolar phase dominates, whereas at faster rates the bipolar phase dominates and at yet faster still rate, aggregation at nonpolar locations occurs. Such a rate dependency may explain differences in the observed patterns reported for PopZ induced expression in E. coli cells. Lastly, we show how such a localization process may aid the segregation of other cellular components such as the replication origin which anchors to a pole. We find that adding extra interactions does not destabilize the polar patterning, nor is it sufficient to drive the localization of the origin and indeed other localization and stabilization mechanisms are required.