Berlin 2008 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 16: Pattern Formation and Developmental Processes
BP 16.3: Vortrag
Mittwoch, 27. Februar 2008, 18:00–18:15, C 243
A stochastic Boolean network model of receptor cross-talk in angiogenesis — •Thimo Rohlf1,2 and Amy L. Bauer3 — 1Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM 87501, USA — 2Max-Planck Institute for Mathematics in the Sciences, Inselstrasse 22, D-04103 Leipzig — 3Los Alamos National Laboratory (T-14), MS B-262, Los Alamos, NM 87545, USA
How cells interpret and synthesize multiple biochemical signals initiated by key external stimuli during angiogenesis, namely growth factors, matrix molecules, and cell-cell communication via cadherins, is a challenging problem. From available databases, we construct a Boolean network model that highlights the cross-talk between growth factor, integrin, and cadherin receptors, and systematically analyze the dynamical stability of the network under continuous-time Boolean dynamics with a noisy production function.
We find that the signal transduction network exhibits robust and fast response to external signals, independent of the internal cell state. We derive an input-output table that maps external stimuli to cell phenotypes, which is extraordinarily stable against molecular noise, with one important exception: an oscillatory feedback-loop between the key signal molecules RhoA and Rac (as sometimes is postulated in the literature) is unstable under arbitrarily low noise, leading to erratic, dysfunctional cell motion. Finally, we show that the network exhibits an apoptotic response rate that increases with noise, suggesting that the probability of programmed cell death increases in response to conflicting or confusing signals.