Epithelia remove excess cells through extrusion, and prevent accumulation of unnecessary or pathological cells. The extrusion process can be triggered by apoptotic signaling1, oncogenic transformation2,3, and overcrowding of cells4–6. Despite the important links of cell extrusion to developmental7, homeostatic5 and pathological processes2,8,9 such as cancer metastasis, its underlying mechanism and connections to the intrinsic mechanics of the epithelium are largely unexplored. Here, we show that apoptotic cell extrusion is provoked by singularities in cell alignments9,10 in the form of comet-like topological defects. We find a universal correlation between the extrusion sites and positions of nematic defects in the cell orientation field in different epithelium types. We model the epithelium as an active nematic liquid crystal and compare numerical simulations to strain rate and stress measurements within cell monolayers. The results confirm the active nematic nature of epithelia for the first time, and demonstrate that defect-induced isotropic stresses are the primary precursor of mechanotransductive responses in cells such as YAP (Yes-associated protein) transcription factor activity11, caspase-3 mediated cell death, and extrusions. Importantly, the defect-driven extrusion mechanism depends on intercellular junctions, since the weakening of cell-cell interactions in α-catenin knockdown (α-catKD) monolayer reduces the defect size and increases both the number of defects and extrusion rates, as also predicted by our model. We further demonstrate the ability to control extrusion hotspots by geometrically inducing defects through microcontact-printing of patterned monolayers. Together we propose a novel mechanism for apoptotic cell extrusion: spontaneously formed topological defects in epithelia govern cell fate. This new finding has important implications in predicting extrusion hotspots and dynamics in vivo, with potential applications to tissue regeneration and metastasis suppression. Moreover, we anticipate that the analogy between the epithelium and active nematic liquid crystals will trigger further investigations of the link between cellular processes and the material properties of epithelia.

The flow properties of a continuum model for an active nematic is studied and compared with recent experiments on suspensions of microtubule bundles and molecular motors. The velocity correlation length is found to be independent of the strength of the activity while the characteristic velocity scale increases monotonically as the activity is increased, both in agreement with the experimental observations. We interpret our results in terms of the creation and annihilation dynamics of a gas of topological defects.Active systems that produce their own energy, such as bacterial suspensions and living cells, are proving rich research areas [1,2]. Apart from their obvious relevance to a quantitative understanding of biological functions, active systems naturally operate out of thermodynamic equilibrium and hence provide a testing ground for theories of non-equilibrium statistical physics [3]. Hydrodynamic instabilities are inherent to active fluids [4][5][6][7][8], and active suspensions spontaneously generate complex flow patterns at length scales much larger than the actual constituents [9][10][11][12][13][14][15][16][17]. These are characterised by strong variations in vorticity (see Fig. 2). Such turbulent-like patterns have been observed in experiments on mixtures of actin or microtubules and motor proteins designed to isolate the important ingredients leading to cellular motility [4,[18][19][20]. Very similar structured flows have been observed in two-dimensional layers of epithelial cells [21] and, at larger length scales, in dense suspensions of swimming bacteria [9][10][11]. The features of the flow have been reproduced qualitatively in simulations of driven rods [22,23] and microswimmers [14][15][16] and in continuum theories of active nematics [11][12][13].The similarity in the hydrodynamic behaviour of the different active experimental and model systems is very appealing, but there are still large gaps in our understanding of the physical mechanisms driving active turbulence. Moreover the extent of and reasons behind any 'universal' behaviour remains unclear [11,24]. To help address these questions in this paper we measure the root mean square (RMS) velocity and velocity-velocity correlation function in a continuum model of an active suspension, as a function of the activity, and compare it to recent experiments on extensile microtubule bundles driven by the motor protein kinesin [4]. This comparison is summarised in Fig.

We study a continuum model of an extensile active nematic to show that mesoscale turbulence develops in two stages: (i) ordered regions undergo an intrinsic hydrodynamic instability generating walls, lines of stong bend deformations, (ii) the walls relax by forming oppositely charged pairs of defects. Both creation and annihilation of defect pairs reinstate nematic regions which undergo further instabilities, leading to a dynamic steady state. We compare this with the development of active turbulence in a contractile active nematic.

Active systems, from bacterial suspensions to cellular monolayers, are continuously driven out of equilibrium by local injection of energy from their constituent elements and exhibit turbulent-like and chaotic patterns. Here we demonstrate both theoretically and through numerical simulations, that the crossover between wet active systems, whose behaviour is dominated by hydrodynamics, and dry active matter where any flow is screened, can be achieved by using friction as a control parameter. Moreover, we discover unexpected vortex ordering at this wet–dry crossover. We show that the self organization of vortices into lattices is accompanied by the spatial ordering of topological defects leading to active crystal-like structures. The emergence of vortex lattices, which leads to the positional ordering of topological defects, suggests potential applications in the design and control of active materials.