Filament Depolymerization Can Explain Chromosome Pulling during Bacterial Mitosis

Chromosome segregation is fundamental to all cells, but the force-generating mechanisms underlying chromosome translocation in bacteria remain mysterious. Caulobacter crescentus utilizes a depolymerization-driven process in which a ParA protein structure elongates from the new cell pole, binds to a ParB-decorated chromosome, and then retracts via disassembly, pulling the chromosome across the cell. This poses the question of how a depolymerizing structure can robustly pull the chromosome that disassembles it. We perform Brownian dynamics simulations with a simple, physically consistent model of the ParABS system. The simulations suggest that the mechanism of translocation is “self-diffusiophoretic”: by disassembling ParA, ParB generates a ParA concentration gradient so that the ParA concentration is higher in front of the chromosome than behind it. Since the chromosome is attracted to ParA via ParB, it moves up the ParA gradient and across the cell. We find that translocation is most robust when ParB binds side-on to ParA filaments. In this case, robust translocation occurs over a wide parameter range and is controlled by a single dimensionless quantity: the product of the rate of ParA disassembly and a characteristic relaxation time of the chromosome. This time scale measures the time it takes for the chromosome to recover its average shape after it is has been pulled. Our results suggest explanations for observed phenomena such as segregation failure, filament-length-dependent translocation velocity, and chromosomal compaction. Author Summary: Reliable chromosome segregation is crucial to all dividing cells. In some bacteria, segregation has been found to occur in a rather counterintuitive way: the chromosome attaches to a filament bundle and erodes it by causing depolymerization of the filaments. Moreover, unlike eukaryotic cells, bacteria do not use molecular motors and/or macromolecular tethers to position their chromosomes. This raises the general question of how depolymerizing filaments alone can continuously and robustly pull cargo as the filaments themselves are falling apart. In this work, we introduce the first quantitative physical model for depolymerization-driven translocation in a many-filament system. Our simulations of this model suggest a novel underlying mechanism for robust translocation, namely self-diffusiophoresis, motion of an object in a self-generated concentration gradient in a viscous environment. In this case, the cargo generates and sustains a concentration gradient of filaments by inducing them to depolymerize. We demonstrate that our model agrees well with existing experimental observations such as segregation failure, filament-length-dependent translocation velocity, and chromosomal compaction. In addition, we make several predictions–including predictions for the specific modes by which the chromosome binds to the filament structure and triggers its disassembly–that can be tested experimentally.