Physical Modeling of Chromosome Segregation in Escherichia coli Reveals Impact of Force and DNA Relaxation

Abstract

The physical mechanism by which Escherichia coli segregates copies of its chromosome for partitioning into daughter cells is unknown, partly due to the difficulty in interpreting the complex dynamic behavior during segregation. Analysis of previous chromosome segregation measurements in E. coli demonstrates that the origin of replication exhibits processive motion with a mean displacement that scales as t(0.32). In this work, we develop a model for segregation of chromosomal DNA as a Rouse polymer in a viscoelastic medium with a force applied to a single monomer. Our model demonstrates that the observed power-law scaling of the mean displacement and the behavior of the velocity autocorrelation function is captured by accounting for the relaxation of the polymer chain and the viscoelastic environment. We show that the ratio of the mean displacement to the variance of the displacement during segregation events is a critical metric that eliminates the compounding effects of polymer and medium dynamics and provides the segregation force. We calculate the force of oriC segregation in E. coli to be ∼0.49 pN.

The Ghost in the Machine: Is the Bacterial Chromosome a Phantom Chain?

“…Lampo et al (5) apply the same model to explain the scaling of the oriC dynamics at long timescales. One would have thought that concurrent processes of chromosome segregation at these long timescales should have major impacts on the oriC motion, because the nucleoid itself-the underlying structure that the oriC moves along-is undergoing dramatic remodeling.…”

“…One would have thought that concurrent processes of chromosome segregation at these long timescales should have major impacts on the oriC motion, because the nucleoid itself-the underlying structure that the oriC moves along-is undergoing dramatic remodeling. Instead, Lampo et al (5) show that the same Rouse model of a DNA polymer driven by an external force fully recapitulates the subdiffusive scaling of oriC motion during chromosome segregation. This means, from the perspective of the chromosome replication origin, that the nucleoid, even through the process of segregation, provides an effectively static viscoelastic background environment similar to that between rounds of chromosome replication.…”

“…Accordingly, it is a general belief that integration of physical and biological approaches is the future paradigm in this, as in many other, biological fields. In this issue of the Biophysical Journal, work from Lampo et al (5) represents a good example of this integrated approach.…”

“…Because the power-law exponent scaling is an indicator of the dynamic organization of the underlying structure, on which the motion takes place, one could extract a great deal of information on the material properties of the structure, in this case the nucleoid itself. The early analytic theory of Lampo et al (5) considers the bacterial chromosome as a Rouse polymer, i.e., a ''phantom'' chain that can run across itself without volume exclusion between its segments (6). This Rouse model is perhaps the simplest polymer model for bacterial chromosomes.…”

Complementary mode analyses between sub- and superdiffusion

“…Many intriguing examples can be observed in the dynamics of complex fluids [7][8][9][10][11][12]. Intracellular transport is a related realm in out-of-equilibrium systems, which is under active investigation in current biophysics studies [4,[13][14][15][16][17][18][19][20]. A time series of stock prices is yet another example, which enters the long list of anomalous diffusion phenomena.…”