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Histochem Cell Biol (2010) 133:405415 DOI 10.1007/s00418-010-0680-3
ORIGINAL PAPER
Tissue stretch induces nuclear remodeling in connective tissue broblasts
Helene M. Langevin Kirsten N. Storch
Robert R. Snapp Nicole A. Bouffard
Gary J. Badger Alan K. Howe Douglas J. Taatjes
Accepted: 11 February 2010 / Published online: 18 March 2010 Springer-Verlag 2010
Abstract Studies in cultured cells have shown that nuclear shape is an important factor inuencing nuclear function, and that mechanical forces applied to the cell can directly affect nuclear shape. In a previous study, we demonstrated that stretching of whole mouse subcutaneous tissue causes dynamic cytoskeletal remodeling with perinuclear redistribution of a-actin in broblasts within the tissue. We have further shown that the nuclei of these broblasts have deep invaginations containing a-actin. In the current study, we
hypothesized that tissue stretch would cause nuclear remodeling with a reduced amount of nuclear invagination, measurable as a change in nuclear concavity. Subcutaneous areolar connective tissue samples were excised from 28 mice and randomized to either tissue stretch or no stretch for 30 min, then examined with histochemistry and confocal microscopy. In stretched tissue (vs. non-stretched), bro-blast nuclei had a larger cross-sectional area (P \ 0.001), smaller thickness (P \ 0.03) in the plane of the tissue, and smaller relative concavity (P \ 0.005) indicating an increase in nuclear convexity. The stretch-induced loss of invaginations may have important inuences on gene expression, RNA trafcking and/or cell differentiation.
Keywords Cytoskeleton Subcutaneous Nucleus
Mechanotransduction Invagination
Introduction
The cell nucleus is increasingly recognized as a highly dynamic organelle whose function is intrinsically linked to its structural organization (Dundr and Misteli 2001). Nuclear shape has been shown to inuence fundamental aspects of nuclear function including chromatin remodeling and gene transcription (Dalby et al. 2007; Itano et al. 2003; Lammerding et al. 2004; Thomas et al. 2002). One of the most dramatic changes in nuclear shape is the folding and unfolding of nuclear invaginations. These structures are thought to play a role in cell differentiation as well as chromatin organization, nucleocytoplasmic transport, calcium signaling and RNA trafcking (Abe et al. 2004; Bloom et al. 1996; Echevarria et al. 2003; Fricker et al. 1997; Johnson et al. 2003). There is also evidence that the commitment of a cell to proliferation or differentiation can