Mitotic waves in an import-diffusion model with multiple nuclei in a shared cytoplasm

Abstract

Nuclei import and export proteins, including cell cycle regulators. These import-export processes are modulated periodically by the cell cycle, for example due to the periodic assembly and breakdown of the nuclear envelope. As such, replicated DNA can be segregated between the two daughter cells and the proteins that were localized in the nucleus are free to diffuse throughout the cytoplasm. Here, we study a mathematical import-diffusion model to show how proteins, i.e. cell cycle regulators, could be redistributed in the cytoplasm by nuclei that periodically toggle between interphase and mitosis. We show that when the cell cycle period depends on the local concentration of regulators, the model exhibits mitotic waves. We discuss how the velocity and spatial origin of these mitotic waves depend on the different model parameters. This work is motivated by recent in vitro experiments reporting on mitotic waves in cycling cell-free extracts made with Xenopus laevis frog eggs, where multiple nuclei share the same cytoplasm. Such experiments have shown that nuclei act as pacemakers for the cell cycle and thus play an important role in collectively defining the spatial origin of mitotic waves.

Keywords: Biological oscillators; Biological physics; Biological traveling waves; Cell cycle dynamics; Pacemaker dynamics; Partial differential equations; Xenopus cell-free extracts; Xenopus laevis early development.