The Long and Viscous Road: Uncovering Nuclear Diffusion Barriers in Closed Mitosis

Abstract: During Saccharomyces cerevisiae closed mitosis, parental identity is sustained by the asymmetric segregation of ageing factors. Such asymmetry has been hypothesized to occur via diffusion barriers, constraining protein lateral exchange in cellular membranes. Diffusion barriers have been extensively studied in the plasma membrane, but their identity and organization within the nucleus remain unknown. Here, we propose how sphingolipid domains, protein rings, and morphological changes of the nucleus may coordinate to restrict protein exchange between nuclear lobes. Our spatial stochastic model is based on several lines of experimental evidence and predicts that, while a sphingolipid domain and a protein ring could constitute the barrier during early anaphase; a sphingolipid domain spanning the bridge between lobes during late anaphase would be entirely sufficient. Additionally, we explore the structural organization of plausible diffusion barriers. Our work shows how nuclear diffusion barriers in closed mitosis may be emergent properties of simple nanoscale biophysical interactions.