Nuclear decoupling is part of a rapid protein-level cellular response to high-intensity mechanical loading
Open accessPublished version of a preprint
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.
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References 84 · Cited by 91
- Authors
- Gilbert, H. T. J., Mallikarjun, V., Dobre, O., Jackson, M. R., Pedley, R., Gilmore, A. P., Richardson, S. M., & Swift, J.
- Affiliations
- Manchester Academic Health Science Centre (GB)
- Corresponding author
- Swift, Joe
- ORCID
- Venue
- Nature Communications
- Published
- 2019-09-12
- Volume
- 10
- Issue
- 1
- Pages
- 4149-4149
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6742657
- OpenAlex
- W2965965670
- Cited by
- 91
- References
- 84
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 14 · 2023: 19 · 2022: 13 · 2021: 8 · 2020: 8 · 2019: 7
- FWCI
- 4.77
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, cc-by)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Wellcome Trust (097820/Z/11/B, 203128/Z/16/Z)
- RCUK | Biotechnology and Biological Sciences Research Council (BB/L024551/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- mechanotransduction, cyclic tensile strain, mesenchymal stem cells, LINC complex, SUN2, post-translational modification, protein conformation, nuclear envelope, substrate stiffness, transcriptional downregulation
- MeSH terms
- Protein Domains, Amino Acid Sequence, Biomechanical Phenomena, Cell Nucleus, Chromatin, Cytoskeleton, DNA Damage, Histones, Humans, Ion Channels, Models, Biological, Nuclear Envelope, Nuclear Proteins, Protein Processing, Post-Translational, RNA, Messenger, Stress, Mechanical, Tensile Strength, Proteome, Cell Nucleus Shape, Mesenchymal Stem Cells
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