Physical descriptions of the bacterial nucleoid at large scales, and their biological implications

Abstract

Recent experimental and theoretical approaches have attempted to quantify the physical organization (compaction and geometry) of the bacterial chromosome with its complement of proteins (the nucleoid). The genomic DNA exists in a complex and dynamic protein-rich state, which is highly organised at various length scales.This has implications for modulating (when not directly enabling) the core biological processes of replication, transcription, segregation. We overview the progress in this area, driven in the last few years by new scientific ideas and new interdisciplinary experimental techniques, ranging from high space-and time-resolution microscopy to high-throughput genomics employing sequencing to map different aspects of the nucleoid-related interactome. The aim of this review is to present the wide spectrum of experimental and theoretical findings coherently, from a physics viewpoint. In particular, we highlight the role that statistical and soft condensed matter physics play in describing this system of fundamental biological importance, specifically reviewing classic and more modern tools from the theory of polymers.We also discuss some attempts towards unifying interpretations of the current results, pointing to possible directions for future investigation.

Short-time movement of E. coli chromosomal loci depends on coordinate and subcellular localization

“…The last decade has provided ample evidence 3,4 that the 'nucleoid', that is, the complex composed of genomic DNA, RNA and associated proteins is highly organized in its dynamics and structure. Chromosome dynamics and organization are intricately entangled with the fundamental physiological processes of genome replication and gene expression, and thus with growth, response to stimuli and ultimately fitness.…”

“…The viscoelastic nature of the bacterial cytosol, and the role of the nucleoid in establishing it are not well characterized 4 . Analysing the thermal motion of tracers embedded within viscoelastic materials is a standard technique in soft-matter physics for extracting material properties 24,25 and for information on its underlying structure (for example, the crosslinking architecture of cytoskeletal polymer networks 26 ).…”

“…Thus, the short-time dynamics of a fluorescent locus contains information about the architecture of its surroundings. At small timescales, the contribution of the dynamics of segregation is negligible, and the observed loci motions should relate more simply to the basic 'polymer solution' properties of the chromosome 4 . This idea is supported by the following estimate.…”

Persistent super-diffusive motion of Escherichia coli chromosomal loci

“…C hromosomal structure and dynamics in bacteria comprises a number of complex entangled phenomena, which has consequently led to a far more primitive understanding of its underlying physical characteristics in comparison to its eukaryotic counterpart [1][2][3] . Much of the complexity is a consequence of the lack of spatial compartments within the cell and a poorly characterized hierarchy in spatiotemporal dynamics throughout the cell cycle.…”

“…The sources of energy driving the segregation process are currently not clear. It is difficult to disentangle the process of segregation from the basal physical nature and organization of the nucleoid 3 . If segregation were a smooth process, it would appear as a drift over the underlying short-timescale subdiffusion.…”