Growing experimental evidence indicates that topological defects could serve as organizing centers in the morphogenesis of tissues. Here, we provide a quantitative explanation for this phenomenon, rooted in the buckling theory of deformable active polar liquid crystals. Using a combination of linear stability analysis and computational fluid dynamics, we demonstrate that active layers, such as confined cell monolayers, are unstable to the formation of protrusions in the presence of disclinations. The instability originates from an interplay between the focusing of the elastic forces, mediated by defects, and the renormalization of the system’s surface tension by the active flow. The posttransitional regime is also characterized by several complex morphodynamical processes, such as oscillatory deformations, droplet nucleation, and active turbulence. Our findings offer an explanation of recent observations on tissue morphogenesis and shed light on the dynamics of active surfaces in general.

Changes in tissue geometry during developmental processes are associated with collective migration of cells. Recent experimental and numerical results suggest that these changes could leverage on the coexistence of nematic and hexatic orientational order at different length scales. How this multiscale organization is affected by the material properties of the cells and their substrate is presently unknown. In this study, we address these questions in monolayers of Madin-Darby canine kidney cells having various cell densities and molecular repertoires. At small length scales, confluent monolayers are characterized by a prominent hexatic order, independent of the presence of E-cadherin, monolayer density, and underlying substrate stiffness. However, all three properties affect the meso-scale tissue organization. The length scale at which hexatic order transits to nematic order, the “hexanematic” crossover scale, strongly depends on cell-cell adhesions and correlates with monolayer density. Our study demonstrates how epithelial organization is affected by mechanical properties, and provides a robust description of tissue organization during developmental processes.

A leading paradigm for understanding the large-scale behavior of tissues is via generalizations of liquid crystal physics; much like liquid crystals, tissues combine fluid-like, viscoelastic behaviors with local orientational order, such as nematic symmetry. Whilst aspects of quantitative agreement have been achieved for flat monolayers, the most striking features of tissue morphogenesis-including symmetry breaking, folding and invagination-concern surfaces with complex curved geometries in three dimensions. As yet, however, characterizing such behaviors has been frustrated due to the absence of proper image analysis methods; current state-of-the-art methods almost exclusively rely on two-dimensional intensity projections of multiple image planes, which superimpose data and lose geometric information that can be crucial. Here, we describe an analysis pipeline that properly captures the nematic order and topological defects associated with tissue surfaces of arbitrary geometry, which we demonstrate in the context of in vitro multicellular aggregates, and in vivo zebrafish hearts.