Enzyme localization, crowding, and buffers collectively modulate diffusion-influenced signal transduction: Insights from continuum diffusion modeling

The Journal of Chemical Physics
Peter M Kekenes-HuskeyJ Andrew McCammon

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 a...Continue Reading

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Citations

Jun 22, 2016·The Journal of Physical Chemistry. B·Peter M Kekenes-HuskeySelcuk Atalay
Jun 26, 2020·PLoS Computational Biology·Hadi RahmaninejadPeter Kekenes-Huskey
May 14, 2016·Physical Review. E·Laurence SignonAnnie Lemarchand
Feb 17, 2018·The Journal of Chemical Physics·Rafael RoaJoachim Dzubiella
May 1, 2019·Proceedings of the National Academy of Sciences of the United States of America·Sören von BülowGerhard Hummer
Oct 20, 2020·Physical Biology·Wasiur R KhudaBukhshGrzegorz A Rempała

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