Retroactivity attenuation through signal transduction cascades
Name
Del Vecchio_Retroactivity attenuation.pdf
Size
737.3 KB
Format
Adobe PDF
Checksum (MD5)
3493dff5cac5ec833d40daf67e39177b
Author(s)
Rivera, Phillip M.
Del Vecchio, Domitilla
Date Issued
June 2014
Journal
Proceedings of the 2014 American Control Conference
Publisher
Institute of Electrical and Electronics Engineers (IEEE)
Citation
Rivera, Phillip M., and Domitilla Del Vecchio. “Retroactivity Attenuation through Signal Transduction Cascades.” 2014 American Control Conference (June 2014).
Version
Author's final manuscript
Abstract
This paper considers the problem of attenuating retroactivity, that is, the effect of loads in biological networks and demonstrates that signal transduction cascades incorporating phosphotransfer modules have remarkable retroactivity attenuation ability. Uncovering the biological mechanisms for retroactivity attenuation is relevant in synthetic biology to enable bottom-up modular composition of complex circuits. It is also important in systems biology for deepening our current understanding of natural principles of modular organization. In this paper, we perform a combined theoretical and computational study of a cascade system comprising two phosphotransfer modules, ubiquitous in eukaryotic signal transduction, when subject to load from downstream targets. Employing singular perturbation on the finite time interval, we demonstrate that this system implements retroactivity attenuation when the input signal is sufficiently slow. Employing trajectory sensitivity analysis about nominal parameters that we have identified from in vivo data, we further demonstrate that the key parameters for retroactivity attenuation are those controlling the timescale of the system.
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1109/ACC.2014.6858840
