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Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus

Nature Reviews Molecular Cell Biology volume 10, pages 75–82 (2009)Cite this article

Abstract

Research in cellular mechanotransduction often focuses on how extracellular physical forces are converted into chemical signals at the cell surface. However, mechanical forces that are exerted on surface-adhesion receptors, such as integrins and cadherins, are also channelled along cytoskeletal filaments and concentrated at distant sites in the cytoplasm and nucleus. Here, we explore the molecular mechanisms by which forces might act at a distance to induce mechanochemical conversion in the nucleus and alter gene activities.

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Figure 1: Structural connectivity and long-distance force propagation.
Figure 2: Mechanotransduction at a distance.
Figure 3: Molecular connectivity from the ECM to the nucleus.
Figure 4: Possible nuclear mechanochemical conversion mechanisms.

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Acknowledgements

The authors thank E. Xuan, A. Maniotis and S. Na for providing Fig. 1a, Fig. 1b,c and Fig. 2b, respectively, and A. Maniotis and J. Karavitis for permission to use their movie of chromosome pulling. This work was supported by grants from the National Institutes of Health (to N.W., J.T. and D.E.I.) and a Department of Defense Breast Cancer Innovator Award (to D.E.I.).

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Authors and Affiliations

  1. Ning Wang is at the Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, 1206 West Green Street, Urbana, Illinois 61801, USA.,

    Ning Wang

  2. Departments of Pathology and Surgery, Jessica D. Tytell and Donald E. Ingber are at the Vascular Biology Program, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.,

    Jessica D. Tytell

  3. Donald E. Ingber is also at the Wyss Institute for Biologically Inspired Engineering and the School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02139, USA.,

    Donald E. Ingber

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  1. Ning Wang
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Correspondence to Donald E. Ingber.

Supplementary information

Supplementary information S1 (movie)| Mechanical continuity in the genome

A movie showing mechanical continuity in the human genome within a living mitotic endothelial cell visualized by harpooning a single chromosome using a glass microneedle, as shown in FIG. 1c and REF. 1 (Kindly provided by A. Maniotis, U. of Illinois at Chicago). (MOV 7508 kb)

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Wang, N., Tytell, J. & Ingber, D. Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat Rev Mol Cell Biol 10, 75–82 (2009). https://doi.org/10.1038/nrm2594

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