Berlin 2012 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 20: Regulation
BP 20.8: Vortrag
Donnerstag, 29. März 2012, 11:45–12:00, H 1058
A kinetic model for RNA interference of focal adhesions — •Max Hoffmann1,2 and Ulrich Schwarz1,2 — 1Bioquant, Heidelberg University, Heidelberg, Germany — 2Institute for Theoretical Physics, Heidelberg University, Heidelberg, Germany
Focal adhesions are integrin-based cell-matrix contacts and transduce and integrate mechanical and biochemical cues from the environment. More than 150 different proteins localize to focal adhesions and have been systematically classified in the adhesome project (www.adhesome.org). First RNAi-screens have been performed for focal adhesions and corroborated the hierarchical structure suggested by the adhesome project. We have developed a kinetic model for RNA interference of the focal adhesion hierarchy with explicit representation of siRNA-concentration and implicit effects of mechanical force. For the first time a link is made between the dynamics of RNA interference and the assembly dynamics of focal adhesions. Our kinetic model shows a variety of features for focal adhesions under the influence of RNA interference. Two basic time scales of the dynamics of RNAi-influenced focal adhesions are verified: a short one for the adaptation of the focal adhesions to changes in the environment, and a much longer one that controls the siRNA-mediated knockdown. A sensitivity analysis provides insight into the response of the focal adhesions to rate or parameter changes. This knowledge can be used to optimize the effect of RNA interference on focal adhesions. We show that different force models can lead to largely differing results.