Regensburg 2013 – scientific programme
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BP: Fachverband Biologische Physik
BP 24: Posters: Physics of Cells
BP 24.9: Poster
Wednesday, March 13, 2013, 17:30–19:30, Poster C
A systems-level model for focal adhesions — •Max Hoffmann1,2 and Ulrich S. Schwarz1,2 — 1BioQuant, Heidelberg University, Heidelberg, Germany — 2Institute for Theoretical Physics, Heidelberg University, Heidelberg, Germany
Focal adhesions are cell-matrix contacts, which transduce and integrate mechanical as well as biochemical cues from the environment. They are large supra-molecular assemblies with more than 170 types of proteins and more than 700 types of interactions collectively known as the "adhesome". Due to their association with the plasma membrane, focal adhesions are spatially organized in three layers of adhesion receptors, connector and signaling molecules, as well as cytoskeletal proteins. The exact composition and function of focal adhesions is strongly regulated by signaling (including the effect of the small GTPases from the Rho family) and the impact of mechanical force.
Here we present theoretical models, which account for all of these features by describing the assembly process of a generic set of core components. First we introduce a kinetic model that allows us to predict the effect of RNA-interference studies on focal adhesions. Depending on the specific knockdown, focal adhesions can get up or down regulated, in good agreement with recent experimental findings. The impact of force on the assembly and maturation process is investigated for different force models (slip and catch bonds) that can lead to markedly different phenotypes. Second we address the maturation of focal adhesions in spatial detail with a particle-based simulation reflecting the spatial-temporal coordination close to the leading edge of the cell.