Inherent Variability in the Kinetics of Autocatalytic Protein Self-Assembly

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Abstract / Description of output

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.

Original languageEnglish
Article number098101
Number of pages5
JournalPhysical Review Letters
Volume113
Issue number9
DOIs
Publication statusPublished - 26 Aug 2014

Keywords / Materials (for Non-textual outputs)

  • SICKLE HEMOGLOBIN POLYMERIZATION
  • AMYLOID FORMATION
  • ACTIN-FILAMENTS
  • MECHANISM
  • MODEL
  • FRAGMENTATION
  • FLUCTUATIONS
  • AGGREGATION
  • PATHWAY

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