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Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structureWe report here that living cells and nuclei are hard-wired such that a mechanical tug on cell surface receptors can immediately change the organization of molecular assemblies in the cytoplasm and nucleus. When integrins were pulled by micromanipulating bound microbeads or micropipettes, cytoskeletal filaments reoriented, nuclei distorted, and nucleoli redistributed along the axis of the applied tension field. These effects were specific for integrins, independent of cortical membrane distortion, and were mediated by direct linkages between the cytoskeleton and nucleus. Actin microfilaments mediated force transfer to the nucleus at low strain; however, tearing of the actin gel resulted with greater distortion. In contrast, intermediate filaments effectively mediated force transfer to the nucleus under both conditions. These filament systems also acted as molecular guy wires to mechanically stiffen the nucleus and anchor it in place, whereas microtubules acted to hold open the intermediate filament lattice and to stabilize the nucleus against lateral compression. Molecular connections between integrins, cytoskeletal filaments, and nuclear scaffolds may therefore provide a discrete path for mechanical signal transfer through cells as well as a mechanism for producing integrated changes in cell and nuclear structure in response to changes in extracellular matrix adhesivity or mechanics.
Document ID
20040173026
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Maniotis, A. J. (Children's Hospital and Harvard Medical School Boston, MA 02115, United States)
Chen, C. S.
Ingber, D. E.
Date Acquired
August 22, 2013
Publication Date
February 4, 1997
Publication Information
Publication: Proceedings of the National Academy of Sciences of the United States of America
Volume: 94
Issue: 3
ISSN: 0027-8424
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: CA-45548
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Cell Biology
Non-NASA Center
NASA Program Space Biology
NASA Discipline Number 40-20