Fluid pumping and active flexoelectricity can promote lumen nucleation in cell assemblies

Abstract

Significance The presence of fluid-filled cavities is a common feature of multicellular structures. Nucleation and growth of such lumens typically involve the pumping of fluid by cells, which relies on active ion transport. In this paper, we use a continuum description of a spherical cell assembly that takes into account fluid pumping, electric currents, and electric fields to explore the physical mechanisms of lumen formation. We highlight the role of the coupling between tissue bending and electric fields, called tissue flexoelectricity, in the lumen-nucleation process. We show, in particular, that understanding lumen formation requires one to consider the combined effects of mechanical, electrical, and hydraulic mechanisms. We discuss the physical mechanisms that promote or suppress the nucleation of a fluid-filled lumen inside a cell assembly or a tissue. We discuss lumen formation in a continuum theory of tissue material properties in which the tissue is described as a 2-fluid system to account for its permeation by the interstitial fluid, and we include fluid pumping as well as active electric effects. Considering a spherical geometry and a polarized tissue, our work shows that fluid pumping and tissue flexoelectricity play a crucial role in lumen formation. We furthermore explore the large variety of long-time states that are accessible for the cell aggregate and its lumen. Our work reveals a role of the coupling of mechanical, electrical, and hydraulic phenomena in tissue lumen formation.