Hydraulic fracturing and active coarsening position the lumen of the mouse blastocyst

Abstract

During mouse pre-implantation development, the formation of the blastocoel, a fluid-filled lumen, breaks the radial symmetry of the blastocyst. The factors that control the formation and positioning of this basolateral lumen remain obscure. We found that accumulation of pressurized fluid fractures cell-cell contacts into hundreds of micrometer-size lumens. These microlumens eventually discharge their volumes into a single dominant lumen, which we model as a process akin to Ostwald ripening, underlying the coarsening of foams. Using chimeric mutant embryos, we tuned the hydraulic fracturing of cell-cell contacts and steered the coarsening of microlumens, allowing us to successfully manipulate the final position of the lumen. We conclude that hydraulic fracturing of cell-cell contacts followed by contractility-directed coarsening of microlumens sets the first axis of symmetry of the mouse embryo.

Surface Tension Controls the Hydraulic Fracture of Adhesive Interfaces Bridged by Molecular Bonds

“…Whether cells and tissues use this physical mechanism to tune adhesion remains to be tested. We speculate that it is compatible with the healing of high tension microlumens at the expense of expanding low tension lumens during early mammalian development [15].…”

“…For instance, increased pressure in the extra-cellular medium, caused by poroelasticity or by active ionic transport, can lead to hydraulic fracture of cell-cell and cell-matrix adhesions [2,11,12]. Hydraulic disengagement of cell-cell junctions is also required during the opening of fluid-filled luminal cavities (luminogenesis) [13][14][15]. Despite this seeming generality, the physical mechanisms that control the hydraulic fracture of adhesive interfaces bridged by molecular bonds have not been examined.…”

Physical basis of lumen shape and stability in a simple epithelium

“…However, we note that this mechanism is predicted to be physically robust and energy efficient relative to pressure-driven growth, which exposes tissues to pressuredriven rupture (Chan et al, 2019;Ruiz-Herrero et al, 2017). Notably, cells in some model systems continue to utilize pressure-independent mechanisms to grow lumens beyond these intermediate stages, for example, by addition of cells or by fusion of smaller lumens (Cerruti et al, 2013;Dumortier et al, 2019). Importantly, when lumens achieve a sufficient diameter, a pressure-driven transition to circular cross-sections will dominate, providing a simple way to generate regular, space-filling shapes like spheres and tubes (Lubarsky and Krasnow, 2003).…”

Cell fate coordinates mechano-osmotic forces in intestinal crypt morphogenesis

“…Multiple cellular processes have been proposed to be curvature-dependent, which could provide such feedback (46), as would mechano-sensitive processes such as force-dependent adherens and tight junction maturation (47,48). Fluid can exert significant morphogenetic forces, as shown in early mouse embryo or lung morphogenesis (23,49,50,51), which are rapidly transmitted spatio-temporally. The manipulation of lumen volume in combination with biophysical modelling, shown here, is thus a powerful tool and could be broadly applicable to other model systems.…”