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The Nucleus pp 13-26 | Cite as

Mechanical Properties of Interphase Nuclei Probed by Cellular Strain Application

  • Jan Lammerding
  • Richard T. Lee
Part of the Methods in Molecular Biology book series (MIMB, volume 464)

Abstract

The mechanical properties of the interphase nucleus have important implications for cellular function and can reflect changes in nuclear envelope structure and/or chromatin organization. Mutations in the nuclear envelope proteins lamin A and C cause several human diseases, such as Emery-Dreifuss muscular dystrophy, and dramatic changes in nuclear stiffness have been reported in cells from lamin A/C-deficient mice. We have developed a cellular strain technique to measure nuclear stiffness in intact, adherent cells and have applied this experimental method to fibroblasts from mouse models of Emery-Dreifuss muscular dystrophy and to skin fibroblasts from laminopathy patients and healthy control subjects. The experimental protocol is based on measuring induced nuclear deformations in cells plated on a flexible silicone substrate; the nuclear stiffness can subsequently be inferred from the ratio of induced nuclear strain to the applied membrane strain. These experiments reveal that lamins A and C are important determinants of nuclear stiffness and that lamin mutations associated with muscular dystrophies and other laminopathies often result in disturbed nuclear stiffness that could contribute to the tissue-specific disease phenotypes.

Keywords

Nucleus Nuclear stiffness Lamin Muscular dystrophy Cell mechanics Strain 

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Copyright information

© Humana Press, a part of Springer Science + Business Media, LLC 2008

Authors and Affiliations

  • Jan Lammerding
    • 1
  • Richard T. Lee
    • 1
  1. 1.Department of Medicine, Cardiovascular DivisionBrigham and Women’s Hospital/Harvard Medical SchoolCambridgeUSA

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