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by Keyword: Intermediate-filaments
Golde, Tom, Pensalfini, Marco, Chahare, Nimesh, Roca-Cusachs, Pere, Wiche, Gerhard, Charras, Guillaume T, Arroyo, Marino, Trepat, Xavier, (2026). Dynamics of supracellular keratin bundling and nuclear uncaging in stretched epithelia Nature Physics ,
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.
JTD Keywords: Behavior, Cell, Intermediate-filaments, Junctions, Microscopy, Network, Phosphorylation, Plectin, Protein
Grolleman, J, van Engeland, NCA, Raza, M, Azimi, S, Conte, V, Sahlgren, CM, Bouten, CVC, (2023). Environmental stiffness restores mechanical homeostasis in vimentin-depleted cells Scientific Reports 13, 18374
Recent experimental evidence indicates a role for the intermediate filament vimentin in regulating cellular mechanical homeostasis, but its precise contribution remains to be discovered. Mechanical homeostasis requires a balanced bi-directional interplay between the cell's microenvironment and the cellular morphological and mechanical state-this balance being regulated via processes of mechanotransduction and mechanoresponse, commonly referred to as mechanoreciprocity. Here, we systematically analyze vimentin-expressing and vimentin-depleted cells in a swatch of in vitro cellular microenvironments varying in stiffness and/or ECM density. We find that vimentin-expressing cells maintain mechanical homeostasis by adapting cellular morphology and mechanics to micromechanical changes in the microenvironment. However, vimentin-depleted cells lose this mechanoresponse ability on short timescales, only to reacquire it on longer time scales. Indeed, we find that the morphology and mechanics of vimentin-depleted cell in stiffened microenvironmental conditions can get restored to the homeostatic levels of vimentin-expressing cells. Additionally, we observed vimentin-depleted cells increasing collagen matrix synthesis and its crosslinking, a phenomenon which is known to increase matrix stiffness, and which we now hypothesize to be a cellular compensation mechanism for the loss of vimentin. Taken together, our findings provide further insight in the regulating role of intermediate filament vimentin in mediating mechanoreciprocity and mechanical homeostasis.© 2023. The Author(s).
JTD Keywords: contributes, dynamics, focal adhesions, forces, mechanotransduction, migration, motility, organization, tissue, Intermediate-filaments