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• W2797706882 abstract "Cell migration is a complex process, requiring coordination of many subcellular processes including membrane protrusion, adhesion, and contractility. For efficient cell migration, cells must concurrently control both transmission of large forces through adhesion structures and translocation of the cell body via adhesion turnover. Although mechanical regulation of protein dynamics has been proposed to play a major role in force transmission during cell migration, the key proteins and their exact roles are not completely understood. Vinculin is an adhesion protein that mediates force-sensitive processes, such as adhesion assembly under cytoskeletal load. Here, we elucidate the mechanical regulation of vinculin dynamics. Specifically, we paired measurements of vinculin loads using a Forster resonance energy transfer-based tension sensor and vinculin dynamics using fluorescence recovery after photobleaching to measure force-sensitive protein dynamics in living cells. We find that vinculin adopts a variety of mechanical states at adhesions, and the relationship between vinculin load and vinculin dynamics can be altered by the inhibition of vinculin binding to talin or actin or reduction of cytoskeletal contractility. Furthermore, the force-stabilized state of vinculin required for the stabilization of membrane protrusions is unnecessary for random migration, but is required for directional migration along a substrate-bound cue. These data show that the force-sensitive dynamics of vinculin impact force transmission and enable the mechanical integration of subcellular processes. These results suggest that the regulation of force-sensitive protein dynamics may have an underappreciated role in many cellular processes." @default.
• W2797706882 created "2018-04-24" @default.
• W2797706882 creator A5006198973 @default.
• W2797706882 creator A5017402732 @default.
• W2797706882 creator A5058249371 @default.
• W2797706882 creator A5075949337 @default.
• W2797706882 date "2018-04-01" @default.
• W2797706882 modified "2023-10-12" @default.
• W2797706882 title "Vinculin Force-Sensitive Dynamics at Focal Adhesions Enable Effective Directed Cell Migration" @default.
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• W2797706882 doi "https://doi.org/10.1016/j.bpj.2018.02.019" @default.
• W2797706882 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5954296" @default.
• W2797706882 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29642037" @default.
• W2797706882 hasPublicationYear "2018" @default.
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