Article

Design of versatile biochemical switches that respond to amplitude, duration, and spatial cues

Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 01/2010; 107(3):1247-52. DOI: 10.1073/pnas.0908647107
Source: PubMed

ABSTRACT Cells often mount ultrasensitive (switch-like) responses to stimuli. The design principles underlying many switches are not known. We computationally studied the switching behavior of GTPases, and found that this first-order kinetic system can show ultrasensitivity. Analytical solutions indicate that ultrasensitive first-order reactions can yield switches that respond to signal amplitude or duration. The three-component GTPase system is analogous to the physical fermion gas. This analogy allows for an analytical understanding of the functional capabilities of first-order ultrasensitive systems. Experiments show amplitude- and time-dependent Rap GTPase switching in response to Cannabinoid-1 receptor signal. This first-order switch arises from relative reaction rates and the concentrations ratios of the activator and deactivator of Rap. First-order ultrasensitivity is applicable to many systems where threshold for transition between states is dependent on the duration, amplitude, or location of a distal signal. We conclude that the emergence of ultrasensitivity from coupled first-order reactions provides a versatile mechanism for the design of biochemical switches.

Download full-text

Full-text

Available from: Azi Lipshtat, Jun 29, 2015
0 Followers
 · 
65 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this paper is to contribute to the basic understanding of neuronal polarization mechanisms by developing and studying a reaction-diffusion model for protein activation and inactivation. In particular we focus on a feedback loop between PI3 kinase and certain GTPases, and study its behaviour in dependence of neurite lengths. We find that if an ultrasensitive activation is included, the model can produce polarization at a critical length as observed in experiments. Symmetry breaking to polarization in the longer neurite is found only if active transport of a substance, in our case active PI3 kinase, is included into the model.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The author describes the Intel486 SL microprocessor and how the features are used to create robust, power managed portable computers. System performance was raised to the 25- and 33-MHz Intel486 DX microprocessor level. The system power consumption was significantly reduced with 3.3-V operation and power management refinements. The core system logic is reduced to at least half that of Intel386 SL microprocessor based systems. The system footprint was reduced from previous systems by the integration of the cache RAM and numeric coprocessor. The power management architecture is compatible with the Intel386 SL microprocessor, providing system vendors an easy upgrade for their systems and achieving a significant power reduction and performance increase
    Compcon Spring '93, Digest of Papers.; 03/1993
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Virtual Cell (VCell) is a unique computational environment for modeling and simulation of cell biology. It has been specifically designed to be a tool for a wide range of scientists, from experimental cell biologists to theoretical biophysicists. The models created with VCell can range from the simple, to evaluate hypotheses or to interpret experimental data, to complex multilayered models used to probe the predicted behavior of spatially resolved, highly nonlinear systems. In this chapter, we discuss modeling capabilities of VCell and demonstrate representative examples of the models published by the VCell users.
    International review of cell and molecular biology 01/2010; 283:1-56. DOI:10.1016/S1937-6448(10)83001-1 · 4.52 Impact Factor