Deep nuclear invaginations linked to cytoskeletal filaments: Integrated bioimaging of epithelial cells in 3D culture

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 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 connected also to both other cells via desmosome adhesion complexes and to the cell's ECM via hemidesmosomes. This finding supports a physical/mechanical link from the desmosomes and hemidesmosomes to the nucleus, which previously was hypothesized but now is visualized for the first time. These unique structures including the nuclear invaginations and the cytoskeletal connectivity to the cell nucleus is consistent with a dynamic reciprocity between the nucleus and the outside of epithelial cells and tissues.

Document Details

Document Type
Pub Defense Publication
Publication Date
Jan 01, 2016
Source ID
10.1242/jcs.190967

Entities

People

  • Alexandre Bruni-cardoso
  • Claire Robertson
  • Claudia S. López
  • Danielle M Jorgens
  • Haina Huang
  • Hildur Palsdottir
  • Jamie L. Inman
  • Ke Xu
  • Manfred Auer
  • Michal Wojcik
  • Mina Bissell
  • Wen-Ting K Tsai

Organizations

  • Lawrence Berkeley National Laboratory
  • National Science Foundation
  • Office of Extramural Research
  • Oregon Health & Science University
  • United States Department of Defense
  • United States Department of Energy
  • University of Campinas
  • Yusuf Hamied Department of Chemistry

Tags

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Nanoscale Plasmonic Nanotechnology
  • Solar Physics

Technology Areas

  • Microelectronics