Abstract
Cellular behaviors such as migration, division, and differentiation rely on precise timing, and yet the molecular events that govern these behaviors are highly stochastic. We investigate regulatory strategies that decrease the timing noise of molecular events. Autoregulatory feedback increases noise. Yet we find that in the presence of regulation by a second species, autoregulatory feedback decreases noise. To explain this finding, we develop a method to calculate the optimal regulation function that minimizes the timing noise. The method reveals that the combination of feedback and regulation minimizes noise by maximizing the number of molecular events that must happen in sequence before a threshold is crossed. We compute the optimal timing precision for all two-node networks with regulation and feedback, derive a generic lower bound on timing noise, and discuss our results in the context of neuroblast migration during Caenorhabditis elegans development.
References
Jun 27, 1991·Nature·L Dirick, K Nasmyth
May 31, 1991·Cell·F R Cross, A H Tinkelenberg
Oct 1, 1974·Proceedings of the National Academy of Sciences of the United States of America·J J Hopfield
Jan 28, 2004·The Journal of Biological Chemistry·Karen CarniolRichard Losick
Dec 2, 2004·Molecular and Cellular Biology·Brandt L SchneiderBruce Futcher
Jan 3, 2006·Molecular Cell·James M BeanFrederick R Cross
Aug 16, 2006·Physical Review Letters·O CampàsJ-F Joanny
Nov 6, 2007·Cell·Iftach NachmanSharad Ramanathan
Nov 22, 2012·Reports on Progress in Physics·Udo Seifert
Nov 12, 2013·Cell·Ni JiAlexander van Oudenaarden
Nov 7, 2014·Developmental Cell·Remco A MentinkHendrik C Korswagen
May 9, 2015·Molecular Systems Biology·Jérémie RouxPeter K Sorger
Oct 22, 2015·Biophysical Journal·Daniel E Tufcea, Paul François
Jan 11, 2017·Proceedings of the National Academy of Sciences of the United States of America·Khem Raj GhusingaAbhyudai Singh
Jun 8, 2018·PLoS Computational Biology·Shivam GuptaAndrew Mugler
Apr 3, 2019·Physical Review. E·Paul J Mlynarczyk, Steven M Abel