Demanding technological applications require combining traditionally conflicting material properties. One such example is the use of double-network (DN) microstructures in hydrogels [1] and metamaterials [2], which overcome the classical stiffness-stretchability trade-off by ensuring energy dissipation through network entanglement and selective failure. Intriguingly, we have observed DN-like mechanisms in epithelial tissues undergoing extreme deformations [3]. Multiscale simulations of geometrically constrained tangles inspired by cytoskeletal intermediate filaments revealed that entanglement-mediated self-organisation ensures large, nonlinear network-scale deformability while limiting filament strain through marked non-affinity [4]. Accounting for crosslink-mediated interactions with other cell components further highlighted that the extent of non-affinity is modulated by the competition between the time scale of cell deformations and crosslinks’ characteristics such as kinetics and failure strength. Lastly, we observed that connected filament tangles from adjacent cells in sheet-like tissues cooperate to promote non-affinity [5]. We posit that these multiscale mechanisms enable cells to reprogramme their emergent mechanics through local cues, switching seamlessly between affinity and non-affinity. This talk will discuss the mechanics of super-stretched epithelial cells in terms of minimal models of interacting cellular components, identifying the building principles of such living systems and anticipating their translation into design criteria for adaptive artificial materials. REFERENCES [1] J.-Y. Sun et al. Highly stretchable and tough hydrogels. Nature, Vol. 489, pp. 133-136, 2012. [2] J.U. Surjadi, B.F.G. Aymon, M. Carton and C.M. Portela. Double-network-inspired mechanical metamaterials. Nature Materials, Vol. 24, pp. 945-954, 2007. [3] E. Latorre et al. Active superelasticity in three-dimensional epithelia of controlled shape. Nature, Vol. 563, pp. 203-208, 2018. [4] M. Pensalfini, T. Golde, X. Trepat and M. Arroyo. Nonaffine mechanics of entangled networks inspired by intermediate filaments. Physical Review Letters, Vol. 131, pp. 058101, 2023. [5] T. Golde et al. A keratin bundling transition uncages the nucleus in stretched epithelia. bioRxiv 2025.