title: Force fluctuations impact kinetics of biomolecular systems.
abstract: A wide array of biological processes occur at rates that vary significantly with force. Instantaneous molecular forces fluctuate due to thermal noise and active processes, leading to concomitant fluctuations in biomolecular rate constants. We demonstrate that such fluctuations have a dramatic effect on the transition kinetics of force-dependent processes. As an illustrative, biologically relevant example, we model the pausing of eukaryotic RNA polymerase as it transcribes nucleosomal DNA. Incorporating force fluctuations in the model yields qualitatively different predictions for the pausing time scales when compared to behavior under the average force alone. We use our model to illustrate the broad range of behaviors that can arise in biomolecular processes that are susceptible to force fluctuations. The fluctuation time scale, which varies significantly for in vivo biomolecular processes, yields very different results for overall rates and dramatically alters the force regime of relevance to the transition. Our results emphasize the importance of transient high-force behavior for determining kinetics in the fluctuating environment of a living cell.
authors.affiliation: Biophysics Program, Stanford University, Stanford, California 94305, USA.
authors.forename: Elena F
authors.initials: EF
authors.lastname: Koslover
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Spakowitz
mesh_terms: D003198:Computer Simulation; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry* / Q000235:genetics*; D007700:Kinetics; D008954:Models, Biological; D008956:Models, Chemical; D013314:Stress, Mechanical; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D004247:DNA; D012321:DNA-Directed RNA Polymerases