Conditions for complex coacervation of the microtubule-associated tau protein predicted from field theoretic simulations

ORAL

Abstract

The microtubule associated tau protein is a highly charged intrinsically disordered protein (IDP) that has been linked to neurodegenerative diseases including Alzheimer’s disease. Recently, tau has been shown to undergo a liquid-liquid phase transition, leading to speculation about how this process may mediate pathological tau fibrillization. To understand the thermodynamic driving forces of this process, we apply a discrete Gaussian-chain polyelectrolyte model and compute thermodynamic observables using a numerical technique known as field theoretic simulation (FTS). Results from FTS for this coarse-grained tau model reveal how the combination of charge distribution, salt concentration, and temperature-dependent excluded volume determine the observed phase diagram. Our results suggest new avenues for simulation to inform experimental design. Finally, we will comment on extensions of the model and applications to other IDPs.

*This work was partially supported by the MRSEC Program of the National Science Foundation and by a grant from the National Institutes of Health

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Presenters

  • James McCarty

    • University of California, Santa Barbara

Authors

  • James McCarty

    • University of California, Santa Barbara

  • Yanxian Lin

    • University of California, Santa Barbara

  • Kris T Delaney

    • University of California, Santa Barbara
    • Material Research Laboratory, University of California, Santa Barbara

  • Glenn Fredrickson

    • University of California, Santa Barbara
    • Chemical Engineering, University of California, Santa Barbara
    • Department of Chemical Engineering, University of California, Santa Barbara

  • Songi Han

    • University of California, Santa Barbara

  • Joan-Emma Shea

    • University of California, Santa Barbara