Fibrillar adhesion dynamics govern the timescales of nuclear mechano-response via the vimentin cytoskeleton;
: Beedle, Amy E. M.; Sharma, Vivek; Oliver-De La Cruz, Jorge; Jaganathan, Anuja; Albajar-Sigalés, Aina; Max, Yavitt F.; Bera, Kaustav; Andreu, Ion; Granero-Moya, Ignasi; Zalvidea, Dobryna; Kechagia, Zanetta; Wiche, Gerhard; Trepat, Xavier; Ivaska, Johanna; Anseth, Kristi S.; Shenoy, Vivek B.; Roca-Cusachs, Pere
Publisher: Springer Nature
: 2026
Nature Materials
: 1476-1122
: 1476-4660
DOI: https://doi.org/10.1038/s41563-026-02590-x
: https://doi.org/10.1038/s41563-026-02590-x
: https://research.utu.fi/converis/portal/detail/Publication/523471590
The cell nucleus is continuously exposed to external signals, of both chemical and mechanical nature. To ensure proper cellular response, cells need to regulate the transmission, timing and duration of these signals. Although such timescale regulation is well described for chemical signals, whether and how it applies to mechanical signals reaching the nucleus is still not fully understood. Here we demonstrate that the formation of fibrillar adhesions locks the nucleus in a mechanically deformed conformation, setting the mechano-response timescale to that of fibrillar adhesion remodelling (~1 h). This process encompasses both mechanical deformation and associated mechanotransduction (such as via YAP), in response to both increased and decreased mechanical stimulation. The underlying mechanism is the anchoring of the vimentin cytoskeleton to fibrillar adhesions and the extracellular matrix through plectin 1f, which maintains nuclear deformation. Our results reveal a mechanism to regulate the timescale of mechanical adaptation, effectively setting a low-pass filter to mechanotransduction.
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This work has been funded by a Sir Henry Wellcome fellowship (210887/Z/18/Z (A.E.M.B.)), funding from the Royal Society (RG\R1\241155 (A.E.M.B.)), funding from the Spanish Ministry of Science and Innovation (PID2022-142672NB-I00 (P.R.-C.)), the European Research Council (grant 101097753 MechanoSynth (P.R.-C.) and Adv-883739 Epifold (X.T.)), the Generalitat de Catalunya (2021 SGR 01425 (P.R.-C.)), the prize ‘ICREA Academia’ for excellence in research (P.R.-C.), Fundació la Marató de TV3 (201936-30-31 (P.R.-C.)), the ‘la Caixa’ Foundation (Agreement LCF/PR/HR20/52400004 (P.R.-C.)), the National Institutes of Health (F31 DK126427 (F.M.Y.)), J a Beatriu de Pinós fellowship (2020-BP 00211 (J.O.-D.L.C.)), the Spanish Ministry for Science and Innovation (FPU21/03952 (A.A.-S.)), the National Science Foundation (CBET 2033723 (K.S.A.)) and the National Institutes of Health (R01 DK120921 (K.S.A.)). The computational work was supported by National Cancer Institute award U54CA261694 (V.B.S.); National Institute of Biomedical Imaging and Bioengineering awards R01EB017753 (V.B.S.) and R01EB030876 (V.B.S.); National Institute of General Medical Sciences award R01GM155943 (V.B.S.); NSF Center for Engineering Mechanobiology Grant CMMI-154857 (V.B.S.); and NSF Grant DMS-2347834 (V.B.S.). J.I. acknowledges funding from the Finnish Cancer Institute (K. Albin Johansson Professorship to J.I.) and Academy of Finland Centre of Excellence program (grant number 346131 (J.I.)). IBEC is a recipient of a Severo Ochoa Award of Excellence from MINCIN.
