A mathematical model for bleb regulation in zebrafish primordial germ cells

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, e.g. 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 toward a specified direction. Little is known about the factors involved in the controlled and directed bleb generation, 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 a homogeneous to a strongly anisotropic 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 Ezrin redistribution accompanying bleb formation.

Keywords: Darcy flow; Diffusion–advection–reaction system; bleb formation; cell polarization; finite elements.