Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Uncovering Nuclear Diffusion Barriers in Closed Mitosis
Eder Zavala, Tatiana Marquez-Lago

Last modified: 2014-03-28


Diffusion barriers are effective means for constraining protein lateral exchange in cellular membranes. In Saccharomyces cerevisiae, diffusion barriers sustain parental identity through asymmetric segregation of ageing factors during closed mitosis. However, the extent to which rapid nuclear geometrical changes during anaphase and diffusion barriers contribute to membrane compartmentalization is controversial. Even though barriers have been extensively studied in the plasma membrane, their identity and organization within the nucleus remain unknown. Based on different lines of experimental evidence, we present an in silico model of the composition and structural organization of nuclear diffusion barriers during anaphase. We developed models of the nucleus representing early and late stages of anaphase and carried out computational simulations testing the plausibility of sphingolipid domains and protein rings composing the nuclear diffusion barrier. Our model predictions are twofold: while in early anaphase a sphingolipid domain and a protein ring at the bud neck work together to compartmentalize the nucleus; in late anaphase, a sphingolipid domain spanning the bridge between nuclear lobes would be entirely sufficient. Moreover, we offer testable predictions regarding the organization of the nuclear diffusion barrier, its protein exclusion properties, and the resulting distinct diffusion regimes. We show how the biophysical properties of sphingolipid domains and protein rings, in coordination with morphological changes of the nucleus throughout anaphase, make them likely and suitable candidates for composing the diffusion barrier. Additionally, our work narrows down options for experimental validation and describes a novel avenue to study diffusion barriers in other biological membranes.


spatial stochastic simulations; diffusion barriers; sphingolipids; compartmentalization