# American Institute of Mathematical Sciences

July  2020, 25(7): 2749-2774. doi: 10.3934/dcdsb.2020030

## No-oscillation theorem for the transient dynamics of the linear signal transduction pathway and beyond

 1 LMAM and School of Mathematical Sciences, Peking University, Beijing 100871, China 2 Department of Bioengineering and Institute of Engineering in Medicine, University of California, San Diego, San Diego, CA 92093-0021, USA

Received  May 2019 Revised  September 2019 Published  July 2020 Early access  April 2020

Understanding the connection between the topology of a biochemical reaction network and its dynamical behavior is an important topic in systems biology. We proved a no-oscillation theorem for the transient dynamics of the linear signal transduction pathway, that is, there are no dynamical oscillations for each species if the considered system is a simple linear transduction chain equipped with an initial stimulation. In the nonlinear case, we showed that the no-oscillation property still holds for the starting and ending species, but oscillations generally exist in the dynamics of intermediate species. We also discussed different generalizations on the system setup. The established theorem will provide insights on the understanding of network motifs and the choice of mathematical models when dealing with biological data.

Citation: Tiejun Li, Tongkai Li, Shaoying Lu. No-oscillation theorem for the transient dynamics of the linear signal transduction pathway and beyond. Discrete & Continuous Dynamical Systems - B, 2020, 25 (7) : 2749-2774. doi: 10.3934/dcdsb.2020030
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##### References:
(a). Illustration of a simplified MAPK signaling cascade. Here ${\rm Raf}^{\rm p}$, ${\rm MEK}^{\rm p}$ and ${\rm ERK}^{\rm p}$ represent the phosphorylated protein kinase. (b). Part of planar cell polarity WNT signaling pathway
The oscillations can appear for the middle species when the system is nonlinear. Shown here is the solution of $q_2$ for a three-node example with quadratic reaction rates
The oscillations can appear for the middle species when the system is nonlinear. Shown here is the solution of $q_2$ for a three-node example with Hill function type reaction rates. The inset figure shows the amplified detail of $q_2$ for $t\in [0, 12]$
Illustration of the linear signal transduction pathway with two branches, where we assume each species has decay but not been plotted here
Counter example which shows the oscillatory behavior for the middle speices in the sub-branches. Left panel: the network topology and reaction rates. Right panel: the history of $q_2$ which shows oscillation. The inset figure shows the amplified detail of $q_2$
Two kinds of more complicate tree-structured networks. Left panel: two levels but with more sub-branches. Right panel: trees with more than two levels
Left panel: matrix A. Right panel: oscillatory behavior of $q_2$. The inset figure shows the amplified detail of $q_2$
Left panel: matrix A. Right panel: oscillatory behavior of $q_4$
Left panel: network topology. Right panel: oscillatory behavior of $q_4$. The inset figure shows the amplified detail of $q_4$
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