Abstract
Mechanical forces influence many aspects of cell behaviour. Forces are detected and transduced into biochemical signals by force-bearing molecular elements located at the cell surface, in adhesion complexes or in cytoskeletal structures. The nucleus is physically connected to the cell surface through the cytoskeleton and the linker of nucleoskeleton and cytoskeleton (LINC) complex, allowing rapid mechanical stress transmission from adhesions to the nucleus. Although it has been demonstrated that nuclei experience force, the direct effect of force on the nucleus is not known. Here we show that isolated nuclei are able to respond to force by adjusting their stiffness to resist the applied tension. Using magnetic tweezers, we found that applying force on nesprin-1 triggers nuclear stiffening that does not involve chromatin or nuclear actin, but requires an intact nuclear lamina and emerin, a protein of the inner nuclear membrane. Emerin becomes tyrosine phosphorylated in response to force and mediates the nuclear mechanical response to tension. Our results demonstrate that mechanotransduction is not restricted to cell surface receptors and adhesions but can occur in the nucleus.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line
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Cell Nucleus / genetics
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Cell Nucleus / physiology*
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Chromatin / metabolism
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Cytoskeletal Proteins
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Cytoskeleton / metabolism
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DNA / metabolism
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Focal Adhesion Kinase 1 / antagonists & inhibitors
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HeLa Cells
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Histone Deacetylase Inhibitors / pharmacology
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Humans
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Hydroxamic Acids / pharmacology
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Mechanotransduction, Cellular / physiology*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism
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Nerve Tissue Proteins / metabolism*
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Nuclear Lamina / physiology
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Phosphorylation
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Proto-Oncogene Proteins c-abl / antagonists & inhibitors
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RNA Interference
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RNA, Small Interfering
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Stress, Mechanical
Substances
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Chromatin
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Cytoskeletal Proteins
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Microtubule-Associated Proteins
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Nerve Tissue Proteins
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Nuclear Proteins
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RNA, Small Interfering
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SUN1 protein, human
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SUN2 protein, human
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SYNE1 protein, human
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emerin
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trichostatin A
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DNA
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Focal Adhesion Kinase 1
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PTK2 protein, human
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Proto-Oncogene Proteins c-abl