Nakamura, FumihikoSong, MiaHartwig, JohnStossel, Thomas2015-03-022014Nakamura, Fumihiko, Mia Song, John H. Hartwig, and Thomas P. Stossel. 2014. “Documentation and Localization of Force-mediated Filamin A Domain Perturbations in Moving Cells.” Nature communications 5 (1): 4656. doi:10.1038/ncomms5656. http://dx.doi.org/10.1038/ncomms5656.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:14065458Endogenously 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 signaling 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.en-USJournal Article2015-03-0210.1038/ncomms5656