Field induced cell proliferation and death in a model epithelium

Abstract

We present a theoretical study of the dynamics of a thick polar epithelium subjected to the action of both an electric and a flow field in a planar geometry. We develop a generalized continuum hydrodynamic description and describe the tissue as a two component fluid system. The cells and the interstitial fluid are the two components and we keep all terms allowed by symmetry. In particular we keep track of the cell pumping activity for both solvent flow and electric current and discuss the corresponding orders of magnitude. We study the growth dynamics of a tissue slab, its steady states and obtain the dependence of the cell velocity, net cell division rate, and cell stress on the flow strength and the applied electric field. We find that finite thickness tissue slabs exist only in a restricted region of phase space and that relatively modest electric fields or imposed external flows can induce either proliferation or death. Our model can be tested in well controlled experiments on in vitro epithelial sheets, which will open the way to systematic studies of field effects on tissue dynamics.

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

“…C, and Ref. [20]). In particular, for a spheroid which typical radius is of the order of the hundred of micrometers 10 −6 r 10 −3 m, our estimates indicate that effects that are relevant at length scales larger than experimentally accessible ones can be neglected to obtain a simpler velocity profile (see App.…”

“…We focus in this paper on the dynamics of a spherical cell aggregate whose typical radius is of the order of the hundred of micrometers: 10 −6 r 10 −3 m. Using experimental data and order-of-magnitude estimations (see Ref. [20] and App. C), we are able to give estimations for the effective lengths L 0 , L 1 and L 2 appearing in Eq.…”

“…Tissue geometry and notation Following Ref. [20], we adopt in this paper a coarse-grained, hydrodynamic description of tissues to study the formation of lumen in a spherical aggregate of cells. In the simplified model we consider here, the tissue is permeated by the interstitial fluid and described in a two-fluid framework.…”

“…An expansion based on symmetry near the homeostatic pressure P c h -defined as the pressure at which cell death exactly compensates cell division in the isotropic state [24] allows us to derive a constitutive equation for the isotropic cell stress σ c (see Ref. [20] for more details). In the quasistatic limit, the elastic stress has relaxed due to cell division and death, and the constitutive equation for the isotropic part reads [25]:…”

“…In this paper, we use a continuum theory of radially polarized cell spheroids to reveal key physical mechanisms underlying lumen formation. This coarse-grained approach is especially suited to study the combined effects of fluid permeation, electric fields and currents, as well as mechanical stresses stemming from cell division and death [19,20]. We show that lumen formation is an active nucleation problem, governed by tissue growth, fluid pumping and active electric effects.…”