A mathematical model for cell polarization in zebrafish primordial germ cells

TL;DR

This paper presents a coupled bulk-surface mathematical model for cell polarization in zebrafish primordial germ cells, linking intracellular flow and membrane protein dynamics to bleb formation and cell migration.

Contribution

It introduces a novel mathematical framework that explains how intracellular flow and Ezrin distribution contribute to cell polarization, supported by analytical and simulation results.

Findings

Model aligns with experimental observations of cell polarization.

Intracellular Darcy flow influences Ezrin distribution and bleb site.

Simulation results support the proposed polarization mechanism.

Abstract

Blebs are cell protrusions generated by local membrane-cortex detachments followed by expansion of the plasma membrane. Blebs are formed by some migrating cells, for example primordial germ cells of the zebrafish. While blebs occur randomly at each part of the membrane in unpolarized cells, a polarization process guarantees the occurrence of blebs at a preferential site and thereby facilitates migration towards a specified direction. Little is known about the factors involved in development and maintenance of a polarized state, yet recent studies revealed the influence of an intracellular flow and the stabilizing role of the membrane-cortex linker molecule Ezrin. Based on this information, we develop and analyse a coupled bulk-surface model describing a potential cellular mechanism by which a bleb could be induced at a controlled site. The model rests upon intracellular Darcy flow and a diffusion-advection-reaction system, describing the temporal evolution from an unpolarized to a stable polarized Ezrin distribution. We prove the well-posedness of the mathematical model and show that simulations qualitatively correspond to experimental observations, suggesting that indeed the interaction of an intracellular flow with membrane proteins can be the cause of the cell polarization.