Abstract
Biochemical reaction networks consisting of coupled enzymes connect substrate signaling events with biological function. Substrates involved in these reactions can be strongly influenced by diffusion “barriers” arising from impenetrable cellular structures and macromolecules, as well as interactions with biomolecules, especially within crowded environments. For diffusion-influenced reactions, the spatial organization of diffusion barriers arising from intracellular structures, non-specific crowders, and specific-binders (buffers) strongly controls the temporal and spatial reaction kinetics. In this study, we use two prototypical biochemical reactions, a Goodwin oscillator, and a reaction with a periodic source/sink term to examine how a diffusion barrier that partitions substrates controls reaction behavior. Namely, we examine how conditions representative of a densely packed cytosol, including reduced accessible volume fraction, non-specific interactions, and buffers, impede diffusion over nanometer length-scales. We find that diffusion barriers can modulate the frequencies and amplitudes of coupled diffusion-influenced reaction networks, as well as give rise to “compartments” of decoupled reactant populations. These effects appear to be intensified in the presence of buffers localized to the diffusion barrier. These findings have strong implications for the role of the cellular environment in tuning the dynamics of signaling pathways.
Document Type
Article
Publication Date
9-7-2015
Digital Object Identifier (DOI)
https://doi.org/10.1063/1.4929528
Funding Information
P.K.H. thanks the American Heart Association (No. 13POST14510036) and the National Institutes of Health (NIH Award No. 1F32HL114365-01A1) for postdoctoral funding. J.A.M. is supported in part by NIH, NBCR, the Center for Theoretical Biophysics (through the National Science Foundation Award No. PHY-0216576), and the Howard Hughes Medical Institute.
Repository Citation
Kekenes-Huskey, Peter M.; Eun, Changsun; and McCammon, J. A., "Enzyme Localization, Crowding, and Buffers Collectively Modulate Diffusion-Influenced Signal Transduction: Insights from Continuum Diffusion Modeling" (2015). Chemistry Faculty Publications. 71.
https://uknowledge.uky.edu/chemistry_facpub/71
Notes/Citation Information
Published in The Journal of Chemical Physics, v. 143, no. 9, article 094103, p. 1-11.
© 2015 AIP Publishing LLC.
This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing. The following article appeared in The Journal of Chemical Physics, v. 143, no. 9, article 094103, p. 1-11 and may be found at http://dx.doi.org/10.1063/1.4929528.