期刊
PHYSICAL REVIEW LETTERS
卷 113, 期 9, 页码 -出版社
AMER PHYSICAL SOC
DOI: 10.1103/PhysRevLett.113.098101
关键词
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资金
- EPSRC [EP/J007404/1]
- EPSRC DTA studentship
- Royal Society University Research Fellowship
- EPSRC [EP/J007404/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/J007404/1] Funding Source: researchfish
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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