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J Cell Sci. 2017 Jan 1;130(1):177-189. doi: 10.1242/jcs.190967. Epub 2016 Aug 5.

Deep nuclear invaginations are linked to cytoskeletal filaments - integrated bioimaging of epithelial cells in 3D culture.

Author information

1
Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS Donner, Berkeley, CA 94720, USA.
2
Department of Biomedical Engineering, Oregon Health and Science University, 3181 Sam Jackson Park Road, Portland, OR 97239, USA.
3
Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
4
Department of Chemistry, University of California, Berkeley, CA 94720, USA.
5
Department of Biochemistry Instituto de Quimica, Universidade de Sao Paulo, Sao Paulo, 05508-000, Brazil.
6
Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA MJBissell@lbl.gov MAuer@lbl.gov.
7
Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS Donner, Berkeley, CA 94720, USA MJBissell@lbl.gov MAuer@lbl.gov.

Abstract

The importance of context in regulation of gene expression is now an accepted principle; yet the mechanism by which the microenvironment communicates with the nucleus and chromatin in healthy tissues is poorly understood. A functional role for nuclear and cytoskeletal architecture is suggested by the phenotypic differences observed between epithelial and mesenchymal cells. Capitalizing on recent advances in cryogenic techniques, volume electron microscopy and super-resolution light microscopy, we studied human mammary epithelial cells in three-dimensional (3D) cultures forming growth-arrested acini. Intriguingly, we found deep nuclear invaginations and tunnels traversing the nucleus, encasing cytoskeletal actin and/or intermediate filaments, which connect to the outer nuclear envelope. The cytoskeleton is also connected both to other cells through desmosome adhesion complexes and to the extracellular matrix through hemidesmosomes. This finding supports a physical and/or mechanical link from the desmosomes and hemidesmosomes to the nucleus, which had previously been hypothesized but now is visualized for the first time. These unique structures, including the nuclear invaginations and the cytoskeletal connectivity to the cell nucleus, are consistent with a dynamic reciprocity between the nucleus and the outside of epithelial cells and tissues.

KEYWORDS:

Cytoskeleton; Extracellular matrix; Human mammary epithelial cells; Integrated bioimaging; Mechanotransduction; Nucleoplasmic reticulum

PMID:
27505896
PMCID:
PMC5394780
DOI:
10.1242/jcs.190967
[Indexed for MEDLINE]
Free PMC Article

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