On the mechanical regulation of epithelial tissue homeostasis

Abstract

Despite recent efforts to understand homeostasis in epithelial tissues, there are many unknowns surrounding this steady state. It is considered to be regulated by mechanoresponse, but unlike for single cells, this remains heavily debated for tissues. Here, we show that changes in matrix stiffness induce a non-equilibrium transition from tubular to squamous Madin-Darby Canine Kidney II tissues. Nonetheless, despite different cell morphologies and densities, all homeostatic tissues display equivalent topologies, which, hence, must be actively targeted and regulated. On the contrary, the mechanoresponse induces dramatic changes in the large-scale organization of the colonies. On stiff gels, this yields an unreported cooperative state of motile cells displaying higher densities than in the arrested homeostatic state. This suggests a more complex relation between cell density and motility than previously anticipated. Our results unequivocally relate the mechanosensitive properties of individual cells to the evolving macroscopic structures, an effect that could be important for understanding the emergent pathologies of living tissues.

Generic principles of space compartmentalization in protocell patterns

“…2a); polygons with more vertices were rare. This observation agrees well with epithelial monolayers [5] and aster patterns in Phallusia oocytes [7] but is in strong contrast to a Voronoi tesselation of PRPs for which the PDF is markedly wider (see Fig. 2a).…”

“…The PDF of perimeters showed a very similar characteristics (Fig. 2b, inset), and both compare favorably to findings on epithelial cell layers on substrates of different rigidity [5]. Notably, all PDFs were independent of the time point at which they were acquired (cf.…”

“…The stunning similarity of protocell patterns to epithelial cell monolayers [5] and aster arrays in Phallusia oocytes [7] suggests that this way of compartmentalization is a conserved feature in biological self-organization. Simulations of aster arrays [7] may even shed light on common self-organization events on microscopic length scales.…”

“…1). Despite being arrested in interphase and protein synthesis being inhibited, the protocell patterns are strikingly similar to epithelial monolayers [5] and spatially ordered arrays in early embryos [6] or oocytes [7]. Protocell assembly and self-organization is a genuine non-equilibrium phenomenon that is disrupted by ATP/GTP depletion, or by blocking the microtubule cytoskeleton dynamics or dynein motors; blocking actomyosin or kinesin motors involved in mitotic spindles had little to no effect [4].…”

Laminin-defined Mechanical Status Modulates Retinal Pigment Epithelium Functionality

“…The topology and morphology of an epithelial monolayer define its mechanical properties (Hannezo et al, 2014;Alt et al, 2017;Kaliman et al, 2021). Hence, we performed morphometric characterisation of the RPE cells in the different regions of the retina (Fig.…”