Proteomics

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Doxycycline-induced SUN2 overexpression in Y-201 MSC cell line

ABSTRACT: Cells resident in tissues must be resilient to the physical demands of their surroundings. Our current understanding of cellular mechano-signalling is largely based on static systems, but these models do not reproduce the dynamic nature of living tissue. Here, we examined the time-resolved response of primary human mesenchymal stem cells (hMSCs) to periods of cyclic tensile strain (CTS). We observed parallels between morphological changes following low-intensity strain (1 hour, 4% CTS at 1 Hz) and responses to increased substrate stiffness. However, as the strain regime was intensified (CTS at ≥ 2 Hz), we characterised a broad, structured and reversible protein-level response, even as transcription was apparently shut down. Regulation of the linker of nucleo- and cytoskeleton (LINC) complex proteins, and specifically of SUN domain-containing protein 2 (SUN2), was found to decouple mechano-transmission within the cell and hence isolate the nucleus from cellular deformation.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Multipotent Stem Cell, Bone Marrow

SUBMITTER: Venkatesh Mallikarjun  

LAB HEAD: Joe Swift

PROVIDER: PXD012863 | Pride | 2019-04-24

REPOSITORIES: Pride

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Publications

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

Gilbert Hamish T J HTJ   Mallikarjun Venkatesh V   Dobre Oana O   Jackson Mark R MR   Pedley Robert R   Gilmore Andrew P AP   Richardson Stephen M SM   Swift Joe J  

Nature communications 20190912 1

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  ...[more]

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