robust signal processing in living cells强劲的信号处理在活细胞.pdfVIP

Robust Signal Processing in Living Cells 1,2 3 4 5 Ralf Steuer *, Steffen Waldherr , Victor Sourjik , Markus Kollmann * 1 Institute for Theoretical Biology, Humboldt University of Berlin, Berlin, Germany, 2 Manchester Interdisciplinary BioCentre, The University of Manchester, Manchester, ¨ ¨ ¨ United Kingdom, 3 Universitat Stuttgart, Institute for Systems Theory and Automatic Control, Stuttgart, Germany, 4 Zentrum fur Molekulare Biologie der Universitat ¨ ¨ ¨ Heidelberg, DKFZ-ZMBH Alliance, Heidelberg, Germany, 5 Heinrich-Heine-Universitat Dusseldorf, Department of Biology, Dusseldorf, Germany Abstract Cellular signaling networks have evolved an astonishing ability to function reliably and with high fidelity in uncertain environments. A crucial prerequisite for the high precision exhibited by many signaling circuits is their ability to keep the concentrations of active signaling compounds within tightly defined bounds, despite strong stochastic fluctuations in copy numbers and other detrimental influences. Based on a simple mathematical formalism, we identify topological organizing principles that facilitate such robust control of intracellular concentrations in the face of multifarious perturbations. Our framework allows us to judge whether a multiple-input-multiple-output reaction network is robust against large perturbations of network parameters and enables the predictive design of perfectly robust