Biology subjects

Chang, M.-H.

Publications and source records attributed to Chang, M.-H..

2 recordsLinked to original sources

bioRxiv2025

Effects of central dogma processes on the compaction and segregation of bacterial nucleoids

The bacterial cytoplasm is characterized by a distinctive membrane-less organelle, the nucleoid, which harbors chromosomal DNA. We investigate the effects of dynamic processes associated with transcription and translation on the structure of this organelle, using coarsegrained molecular dynamics (MD) simulations implemented with out-of-equilibrium reactions. Our model captures the scale of the entire cell and incorporates a reaction-diffusion system for ribosomes and polyribosomes, combining their out-of-equilibrium dynamics with excluded volume interactions with DNA. Our findings demonstrate that out-of-equilibrium reactions increase the size of the nucleoid. In addition, we show that the nucleoid size increase is proportional to transcriptional activity. Our model reproduces the time-dependent change in nucleoid size observed in rifampicin treatment experiments, where the pool of polyribosomes is depleted. Furthermore, we find these active processes are essential for complete sister chromosome separation and correct nucleoid positioning within the cell. Overall, our study reveals the effects of the central dogma processes on the internal organization and localization of bacterial nucleoids. SignificanceUnderstanding how bacteria organize their chromosomes is fundamental to cell biology. Through our coarse-grained molecular dynamics simulations incorporating out-of-equilibrium processes of transcription and translation, we are able to capture the effects of these central dogma processes on DNA organization and demonstrate that these active biological processes expand the nucleoid and facilitate the separation of daughter chromosomes. Our simulations are compared to experimental measurements and highlight the impact of the out-of-equilibrium conditions of the living cell. These findings point out the crucial interplay between physical forces and biological activity in cellular organization, suggesting that cellular structure depends on non-equilibrium processes.

biophysics↗

bioRxiv2025

The role of active mRNA-ribosome dynamics and closing constriction in daughter chromosome separation in Escherichia coli

The mechanisms by which two sister chromosomes separate and partition into daughter cells in bacteria remain poorly understood. A recent theoretical model has proposed that out-of-equilibrium central dogma reactions involving mRNA and ribosomes play a significant role in this process. Here we test this idea in the Escherichia coli model system using high-throughput fluorescence microscopy in microfluidic devices. We compare our experimental observations with predictions from a reaction-diffusion model that includes central dogma-related reactions and excluded volume interactions between ribosomal subunits, polysomes, and chromosomal DNA. Our results show that the non-equilibrium reactions of ribosomes cause them to aggregate at the midcell, and this process facilitates the separation of the two daughter chromosomes. However, the observed effects are weaker in live cells than our one-dimensional reaction-diffusion model predicts. Rather than relying solely on active mRNA-ribosome dynamics, our data suggest that the closing division septum via steric interactions and potentially entropic forces between two DNA strands coupled to cell elongation act as additional mechanisms to ensure faithful partitioning of the nucleoids to two daughter cells. SignificanceThe mitotic spindle separates chromosomes in eukaryotic cells, but bacteria lack this structure. It remains unclear how bacterial chromosomes partition before cell division. It has been hypothesized that non-equilibrium dynamics of polysomes, that is, mRNA-ribosome complexes, actively drive the separation of bacterial chromosomes. Using quantitative microscopy combined with computational modeling, we show that polysome dynamics facilitates the separation of daughter chromosomes in Escherichia coli, but this process does not constitute the sole mechanism. Our findings suggest that the closing division septum via steric interactions and potentially entropic forces between the two DNA strands act as additional mechanisms.

biophysics↗