Studying the limitations of Michaelis Menten approximation to describe cell signaling dynamics

ALEJANDRA VENTURA; JULIANA REVES SZEMERE; HORACIO ROTSTEIN

Congreso; StatPhys; 2019

In many biological contexts it isimportant to understand how the cell signaling system responds totime-dependent inputs. Signaling pathways stimulated by inputs thatchange rapidly over time need to process a significant amount ofinformation. How much information they can process per unit of timeis proportional to its bandwidth, which can be determined bymeasuring the system?s response to fluctuating signals atdifferent frequencies. The larger the bandwidth of a pathway,the shorter its response time and the more accurately a signallingsystem responds to a rapidly varying signal. The capability ofprocessing temporal information is related to what is known asfrequency encoding.Itis very common to use the Michaelis Menten (MM) approximation tomathematically describe enzymatic reactions. In this way, themodel?s dimensionality is reduced with respect to the mechanisticdescription obtained by using the law of mass action. The MMapproximation distinguishes between the fast and slow dynamicsrelated to the complex and product formation, respectively. Thepresence of this time-scale separation allows for aquasi-steady-state approximation, capturing the latter process.Inthis work we study covalent modification cycles, which are composedof two enzymatic reactions. We focus on the cycles capability ofprocess and transmit temporal information, and the impact of applyingthe MM approximation to these cycles when they receive time-dependentstimuli. We find that the use of the MM approximation always resultsin monotonic time courses, as opposed of adaptive ones, precluding apreference in the frequency response of the cycle. p { margin-bottom: 0.25cm; border: none; padding: 0cm; direction: ltr; color: #000000; line-height: 120%; text-align: left; orphans: 2; widows: 2 }p.western { font-family: "Arial", serif; so-language: en-US }p.cjk { font-family: "Arial" }p.ctl { font-family: "Arial" }