title: Cascading signaling pathways improve the fidelity of a stochastically and deterministically simulated molecular RS latch.
abstract: BACKGROUND
  While biological systems have often been compared with digital systems, they differ by the strong effect of crosstalk between signals due to diffusivity in the medium, reaction kinetics and geometry. Memory elements have allowed the creation of autonomous digital systems and although biological systems have similar properties of autonomy, equivalent memory mechanisms remain elusive. Any such equivalent memory system, however, must silence the effect of crosstalk to maintain memory fidelity.
  
  
  RESULTS
  Here, we present a system of enzymatic reactions that behaves like an RS latch (a simple memory element in digital systems). Using both a stochastic molecular simulator and ordinary differential equation simulator, we showed that crosstalk between two latches operating in the same spatial localization disrupts the memory fidelity of both latches. Crosstalk was reduced or silenced when simple reaction loops were replaced with multiple step or cascading reactions, showing that cascading signaling pathways are less susceptible to crosstalk.
  
  
  CONCLUSIONS
  Thus, the common biological theme of cascading signaling pathways is advantageous for maintaining the fidelity of a memory latch in the presence of crosstalk. The experimental implementation of such a latch system will lead to novel approaches to cell control using synthetic proteins and will contribute to our understanding of why cells behave differently even when given the same stimulus.
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, Ontario, M5S 3G9, Canada. e.mills@utoronto.ca
authors.forename: Evan
authors.initials: E
authors.lastname: Mills
authors.forename: Kevin
authors.initials: K
authors.lastname: Truong
mesh_terms: D016248:Computer Storage Devices; D004798:Enzymes / Q000378:metabolism; D008954:Models, Biological; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction; D013269:Stochastic Processes
chemical_list: D004798:Enzymes; D011506:Proteins