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Title: Deep nuclear invaginations are linked to cytoskeletal filaments – integrated bioimaging of epithelial cells in 3D culture

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 growtharrested 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. Also, the cytoskeleton is 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.
Authors:
ORCiD logo [1] ;  [2] ;  [3] ;  [2] ; ORCiD logo [4] ;  [4] ;  [3] ;  [5] ;  [6] ;  [2] ;  [7] ; ORCiD logo [4]
  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division; Oregon Health and Science Univ., Portland, OR (United States). Dept. of Biomedical Engineering
  2. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division
  3. Univ. of California, Berkeley, CA (United States). Dept. of Chemistry
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division
  5. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Univ. of Sao Paulo (Brazil). Dept. of Biochemistry, Inst. of Chemistry
  6. Oregon Health and Science Univ., Portland, OR (United States). Dept. of Biomedical Engineering
  7. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrated Bioimaging Division; Univ. fo California, Berkeley, CA (United States). Dept. of Chemistry
Publication Date:
Grant/Contract Number:
AC02-05CH11231; P01GM051487; R01CA064789; U54CA143836I
Type:
Published Article
Journal Name:
Journal of Cell Science
Additional Journal Information:
Journal Volume: 130; Journal Issue: 1; Journal ID: ISSN 0021-9533
Research Org:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Institutes of Health (NIH)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; integrated bioimaging; cytoskeleton; mechanotransduction; human mammary epithelial cells; nucleoplasmic reticulum; extracellular matrix
OSTI Identifier:
1337799
Alternate Identifier(s):
OSTI ID: 1379655