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Biphasic responses are encountered at all levels in biological systems. At the cellular level, biphasic dose-responses are widely encountered in cell signaling and post-translational modification systems and represent safeguards against overactivation or overexpression of species. In this paper, we provide a unified theoretical synthesis of biphasic responses in cell signaling systems, by assessing signaling systems ranging from basic biochemical building blocks to canonical network structures to well-characterized exemplars on one hand, and examining different types of doses on the other. By using analytical and computational approaches applied to a range of systems across levels (described by broadly employed models), we reveal (i) design principles enabling the presence of biphasic responses, including in almost all instances, an explicit characterization of the parameter space (ii) structural factors which preclude the possibility of biphasic responses (iii) different combinations of the presence or absence of enzyme-biphasic and substrate-biphasic responses, representing safeguards against overactivation and overexpression, respectively (iv) the possibility of broadly robust biphasic responses (v) the complete alteration of signaling behavior in a network due to biphasic interactions between species (biphasic regulation) (vi) the propensity of different co-existing biphasic responses in the Erk signaling network. These results both individually and in totality have a number of important consequences for systems and synthetic biology.
Pubmed ID: 38054655
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Multi paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.
View all literature mentionsSoftware application for simulation and analysis of biochemical network models and their dynamics. COPASI supports models in the SBML standard and can simulate their behavior using ODEs or Gillespies stochastic simulation algorithm. Arbitrary discrete events can be included in such simulations. Models in COPASI are based on reactions that convert a set of species into another set of species. Simulation can be performed either with stochastic kinetics or with differential equations. COPASI also includes various methods of analysis and data visualization.
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