Inherent variability in the kinetics of autocatalytic protein self-assembly.

نویسندگان

  • Juraj Szavits-Nossan
  • Kym Eden
  • Ryan J Morris
  • Cait E MacPhee
  • Martin R Evans
  • Rosalind J Allen
چکیده

In small volumes, the kinetics of filamentous protein self-assembly is expected to show significant variability, arising from intrinsic molecular noise. This is not accounted for in existing deterministic models. We introduce a simple stochastic model including nucleation and autocatalytic growth via elongation and fragmentation, which allows us to predict the effects of molecular noise on the kinetics of autocatalytic self-assembly. We derive an analytic expression for the lag-time distribution, which agrees well with experimental results for the fibrillation of bovine insulin. Our expression decomposes the lag-time variability into contributions from primary nucleation and autocatalytic growth and reveals how each of these scales with the key kinetic parameters. Our analysis shows that significant lag-time variability can arise from both primary nucleation and from autocatalytic growth and should provide a way to extract mechanistic information on early-stage aggregation from small-volume experiments.

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عنوان ژورنال:
  • Physical review letters

دوره 113 9  شماره 

صفحات  -

تاریخ انتشار 2014