Asymmetrical inheritance of plasmids depends on dynamic cellular geometry and volume exclusion effects

TL;DR

This study investigates how cellular shape changes and volume exclusion influence the asymmetric inheritance of plasmids in yeast, showing that active diffusion barriers are not necessary for this process.

Contribution

It introduces a stochastic spatial model incorporating cell morphology and plasmid size, revealing mechanisms behind plasmid segregation without diffusion barriers.

Findings

Asymmetrical inheritance occurs without active diffusion barriers.

Cell morphology and plasmid size significantly affect segregation.

Modeling confirms passive diffusion suffices for asymmetry.

Abstract

The asymmetrical inheritance of plasmid DNA, as well as other cellular components, has been shown to be involved in replicative aging. In Saccharomyces cerevisiae, there is an ongoing debate regarding the mechanisms underlying this important asymmetry. Currently proposed models suggest it is established via diffusion, but differ on whether a diffusion barrier is necessary or not. However, no study so far incorporated key aspects to segregation, such as dynamic morphology changes throughout anaphase or plasmids size. Here, we determine the distinct effects and contributions of individual cellular variability, plasmid volume and moving boundaries in the asymmetric segregation of plasmids. We do this by measuring cellular nuclear geometries and plasmid diffusion rates with confocal microscopy, subsequently incorporating this data into a growing domain stochastic spatial simulator. Our modelling and simulations confirms that plasmid asymmetrical inheritance does not require an active barrier to diffusion, and provides a full analysis on plasmid size effects.