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Dresden 2020 – scientific programme

The DPG Spring Meeting in Dresden had to be cancelled! Read more ...

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BP: Fachverband Biologische Physik

BP 31: Computational Biophysics (joint session BP/CPP)

BP 31.2: Talk

Thursday, March 19, 2020, 09:45–10:00, SCH A251

Talin impacts force-induced vinculin activation by 'loosening' the vinculin inactive stateFlorian Franz1,2 and •Frauke Gräter1,21HITS gGmbH, Schloß-Wolfsbrunnenweg 35, 69118 Heidelberg, Germany — 2IWR - Interdisciplinary Center for Scientific Computing, Im Neuenheimer Feld 368, 69120, Heidelberg, Germany

Focal Adhesions (FA) are large, multi-protein complexes connecting the cytoskeleton to the extracellular matrix. Their adhesive functionality is tightly regulated by mechanical stress. A key component of FA-associated mechanosensing is vinculin, which can assume either a closed ("inactive") or open ("active") conformation. The underlying activation mechanism, however, remains yet to be fully understood.

Here, we employ molecular dynamics (MD) simulation to demonstrate that vinculin activation is greatly facilitated by the binding of vinculin on talin's vinculin binding site. Steered MD simulations reveal that the force required for activation is drastically reduced upon formation of the vinculin-talin complex. Using correlated motions and force distribution analysis, we illuminate how the force propagation through vinculin changes upon complex formation. Interestingly, after talin dissociation, vinculin returns to its native conformation on a submicrosecond time scale, with 60% of its native contacts restored.

Our results suggest a rapid dynamic equilibrium between 'tight' and 'loosened' inactive vinculin, which depends on talin and determines the level of mechanical stress required for activation. Our study has important implications for our understanding of mechano-sensing mechanisms at FAs.

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