Inherent variability in the kinetics of autocatalytic protein self-assembly (CROSBI ID 220156)
Prilog u časopisu | Pismo (znanstveno) | međunarodna recenzija
Podaci o odgovornosti
Szavits-Nossan, Juraj ; Eden Kym ; Morris, Ryan J. ; MacPhee, Cait E. ; Evans, Martin R. ; Rosalind, Allen J.
engleski
Inherent variability in the kinetics of autocatalytic protein self-assembly
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.
Proteins; Self-Assembly; Kinetics; Fluctuations
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Podaci o izdanju
113
2014.
098101-1-098101-5
objavljeno
0031-9007
10.1103/PhysRevLett.113.098101