Analytical model for macromolecular partitioning during yeast cell division.
BACKGROUND
Asymmetric cell division, whereby a parent cell generates two sibling cells with unequal content and thereby distinct fates, is central to cell differentiation, organism development and ageing. Unequal partitioning of the macromolecular content of the parent cell - which includes proteins, DNA, RNA, large proteinaceous assemblies and organelles - can be achieved by both passive (e.g. diffusion, localized retention sites) and active (e.g. motor-driven transport) processes operating in the presence of external polarity cues, internal asymmetries, spontaneous symmetry breaking, or stochastic effects. However, the quantitative contribution of different processes to the partitioning of macromolecular content is difficult to evaluate.


RESULTS
Here we developed an analytical model that allows rapid quantitative assessment of partitioning as a function of various parameters in the budding yeast Saccharomyces cerevisiae. This model exposes quantitative degeneracies among the physical parameters that govern macromolecular partitioning, and reveals regions of the solution space where diffusion is sufficient to drive asymmetric partitioning and regions where asymmetric partitioning can only be achieved through additional processes such as motor-driven transport. Application of the model to different macromolecular assemblies suggests that partitioning of protein aggregates and episomes, but not prions, is diffusion-limited in yeast, consistent with previous reports.


CONCLUSIONS
In contrast to computationally intensive stochastic simulations of particular scenarios, our analytical model provides an efficient and comprehensive overview of partitioning as a function of global and macromolecule-specific parameters. Identification of quantitative degeneracies among these parameters highlights the importance of their careful measurement for a given macromolecular species in order to understand the dominant processes responsible for its observed partitioning.
Abteilung Systemische Zellbiologie, Max-Planck-Institut für molekulare Physiologie, Otto-Hahn-Str. 11, Dortmund 44227, Germany.
Ali
A
Kinkhabwala
Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH) and Deutsches Krebsforschungszentrum (DKFZ), DKFZ-ZMBH-Allianz, Im Neuenheimer Feld 282, Heidelberg 69120, Germany.
Anton
A
Khmelinskii
Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH) and Deutsches Krebsforschungszentrum (DKFZ), DKFZ-ZMBH-Allianz, Im Neuenheimer Feld 282, Heidelberg 69120, Germany.
Michael
M
Knop
Asymmetric cell division; Bud neck; Cellular transport processes; Diffusion; ERC; Extrachromosomal rDNA circle; NPC; Narrow escape; Nuclear pore complex; Organelle inheritance; Organelle segregation; Prion; Protein aggregate; Yeast mitosis