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Documentation and localization of force-mediated filamin A domain perturbations in moving cells

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  • Fumihiko Nakamura

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Mia Song

    (Brigham and Women’s Hospital, Harvard Medical School)

  • John H. Hartwig

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Thomas P. Stossel

    (Brigham and Women’s Hospital, Harvard Medical School)

Abstract

Endogenously and externally generated mechanical forces influence diverse cellular activities, a phenomenon defined as mechanotransduction. Deformation of protein domains by application of stress, previously documented to alter macromolecular interactions in vitro, could mediate these effects. We engineered a photon-emitting system responsive to unfolding of two repeat domains of the actin filament (F-actin) crosslinker protein filamin A (FLNA) that binds multiple partners involved in cell signalling reactions and validated the system using F-actin networks subjected to myosin-based contraction. Expressed in cultured cells, the sensor-containing FLNA construct reproducibly reported FLNA domain unfolding strikingly localized to dynamic, actively protruding, leading cell edges. The unfolding signal depends upon coherence of F-actin-FLNA networks and is enhanced by stimulating cell contractility. The results establish protein domain distortion as a bona fide mechanism for mechanotransduction in vivo.

Suggested Citation

  • Fumihiko Nakamura & Mia Song & John H. Hartwig & Thomas P. Stossel, 2014. "Documentation and localization of force-mediated filamin A domain perturbations in moving cells," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5656
    DOI: 10.1038/ncomms5656
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