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Nuclear decoupling is part of a rapid protein-level cellular response to high-intensity mechanical loading

Author

Listed:
  • Hamish T. J. Gilbert

    (Wellcome Centre for Cell-Matrix Research
    University of Manchester)

  • Venkatesh Mallikarjun

    (Wellcome Centre for Cell-Matrix Research
    University of Manchester)

  • Oana Dobre

    (Wellcome Centre for Cell-Matrix Research
    University of Manchester
    University of Glasgow)

  • Mark R. Jackson

    (Wellcome Centre for Cell-Matrix Research
    University of Manchester
    Institute of Cancer Sciences)

  • Robert Pedley

    (Wellcome Centre for Cell-Matrix Research
    University of Manchester)

  • Andrew P. Gilmore

    (Wellcome Centre for Cell-Matrix Research
    University of Manchester)

  • Stephen M. Richardson

    (University of Manchester)

  • Joe Swift

    (Wellcome Centre for Cell-Matrix Research
    University of Manchester)

Abstract

Studies of cellular mechano-signaling have often utilized static models that do not fully replicate the dynamics of living tissues. Here, we examine the time-dependent response of primary human mesenchymal stem cells (hMSCs) to cyclic tensile strain (CTS). At low-intensity strain (1 h, 4% CTS at 1 Hz), cell characteristics mimic responses to increased substrate stiffness. As the strain regime is intensified (frequency increased to 5 Hz), we characterize rapid establishment of a broad, structured and reversible protein-level response, even as transcription is apparently downregulated. Protein abundance is quantified coincident with changes to protein conformation and post-translational modification (PTM). Furthermore, we characterize changes to the linker of nucleoskeleton and cytoskeleton (LINC) complex that bridges the nuclear envelope, and specifically to levels and PTMs of Sad1/UNC-84 (SUN) domain-containing protein 2 (SUN2). The result of this regulation is to decouple mechano-transmission between the cytoskeleton and the nucleus, thus conferring protection to chromatin.

Suggested Citation

  • Hamish T. J. Gilbert & Venkatesh Mallikarjun & Oana Dobre & Mark R. Jackson & Robert Pedley & Andrew P. Gilmore & Stephen M. Richardson & Joe Swift, 2019. "Nuclear decoupling is part of a rapid protein-level cellular response to high-intensity mechanical loading," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11923-1
    DOI: 10.1038/s41467-019-11923-1
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