Dynamics of supracellular keratin bundling and nuclear uncaging in stretched epithelia

Abstract There is broad consensus that intermediate filaments, such as keratin, play a key role in protecting cells and tissues from large deformations. However, little is known about how they fulfil this function. Here we show that epithelial cells slowly adapt to stretching through a coupling of a star-bundling transition of keratin filaments with the escape of the nucleus from its keratin cage. The bundling transition begins with a depletion of keratin filaments at tricellular junctions followed by a progressive accumulation in thick bundles that bisect cell–cell junctions. Bundling is a cooperative process that initiates in a few scattered cells and propagates to their neighbours, leading to the growth of multicellular clusters that contain a percolated network of thick keratin bundles. Bundling dynamics are slow and strongly influenced by the interaction between actin and keratin. Informed by a computational model, we provide evidence that keratin bundling generates a compressive stress on the nucleus, which is relaxed by nuclear escape from the keratin cage. The topological transitions identified here provide epithelia with a multiscale mechanism to adapt to sustained stretching.