A dialog between cell adhesion and topology at the core of morphogenesis

TL;DR

It is shown that a local, pair-wise property defined at the cell-cell contact level has important global consequences for embryonic tissue topology, being determinant in defining both the geometric and material properties of early embryo tissues.

Abstract

During the development of an organism, cells must coordinate and organize to generate the correct shape, structure, and spatial patterns of tissues and organs, a process known as morphogenesis. The morphogenesis of embryonic tissues is supported by multiple processes that induce the precise physical deformations required for tissues to ultimately form organs with complex geometries. Among the most active players shaping the morphogenetic path are fine-tuned changes in cell adhesion. In this paper, we show that a local, pair-wise property defined at the cell-cell contact level has important global consequences for embryonic tissue topology, being determinant in defining both the geometric and material properties of early embryo tissues.

Figures (4)

• Figure 1: Different packings of spheres with their geometry (top) and their associated topologies (bottom). For the sake of simplicity, we only show connected configurations ---i.e., with no isolated spheres. With 2 spheres, only one configuration is possible. With 3 spheres, 2 topological configurations are possible, the spheres aligned or arranged in a triangle. Note that the first and the second packings of 3 spheres have different geometries ---in the second one a sphere is twisted upwards--- but the same topology, because the structure of contacts is the same ---a line. With 4 spheres we have 5 different connected topologies in 3D. If the packing topology changes along a given process, either due to external factors or due to changes in the mechanical properties of the spheres, we say that there has been a topological transition.
• Figure 2: Cell adhesion between cells. A) View of cell adhesion at different scales of description: micro (membrane level), meso (cell--cell level), and macro (tissue level with connectivity map). B) Changes in cell geometry induced by cell adhesion, characterized by the relative surface tension $\alpha$, observed through the geometrical relationship between intercellular angle $\theta$. C) Topological transition in which cells form a new connection at a critical value due to a reduction in surface tension $\alpha$. Top: geometrical representation of the cell configuration and associated changes in intercellular angle $\theta$. Bottom: Topological representation of the same transition, in which a new link is created.
• Figure 3: Biological implications of topological transitions. A) Temporal evolution of the relative surface tension $\alpha$ during early mouse embryo development Fabreges:2024. Changes in $\alpha$ have a measurable impact on cell compaction, as observed in experimental 3D confocal reconstructions of the embryo, and at the topological level through the formation of new links in the contact network. This topological transition can be understood and simulated (bottom) by taking into account the experimentally observed changes in cell adhesion $\alpha$ (top). Imaging data of real embryos from T. Hiiragi's lab. (Scale bar, 25 $\mu m$) B) Temporal evolution of the relative surface tension $\alpha$ during zebrafish embryo development Petridou:2021Rustarazo:2025. Variations in $\alpha$ lead to measurable changes in tissue configuration, as observed experimentally using 2D confocal images, and tissue properties as reflected in network rigidity, where the Giant Rigid Cluster (in red) can either span the entire tissue or cover only a small fraction of it, depending on the relative surface tension $\alpha$. These topological rigid-floppy configurations can be understood and simulated (bottom) by taking into account the experimentally observed values in cell adhesion $\alpha$ (top). Imaging data of real embryo tissues from N. Petridou's lab.
• Figure 4: Tissue properties driven by cell adhesion. A) Tissue rigidity transition observed through the phase transition of the Giant Rigid Cluster as a function of the relative surface tension $\alpha$Rustarazo:2025. B) Formation of tricellular junctions in the tissue, defined as the closure of triangular configurations without interstitial fluid, which also undergoes a transition as a function of the relative surface tension $\alpha$, interestingly occurring at the same critical value $\alpha_c$ for GRC Rustarazo:2025. C) Quantification of interstitial fluid in tissues as a function of the relative surface tension $\alpha$, revealing two critical points associated with the closure of triangular configurations ($\alpha_c$, tricellular junction formation) and with the corresponding to the closure of residual 3-dimensional fluid pockets where interstitial fluid remains trapped ($\alpha'_c$, 3D pocket closure) Autorino:2025. D) Surface evolver simulations showing the tissue response to applied pressure, comparing configurations with interstitial fluid to those with closed TCJs. Network size: $25\times 25$, average statistics over 20 replicas, $\alpha=0.92$ for tissue simulation with open TCJs (blue) and $\alpha=0.7$ for tissue simulation with closed TCJs (red), shaded region standard deviation. E) Phase diagram of the tissue states as a function of cell density and relative surface tension. Experimental and simulated tissue configurations are shown across the different regions defined by the critical values ($\phi_c$, $\alpha_c$). The cell-cell contact network is shown in white and the GRC is highlighted in red. Note that relative surface tension, reflecting cell adhesion, is a better indicator of tissue viscosity and rigidity. Imaging data of real embryo tissues from N. Petridou's lab.