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

Autori
Szavits-Nossan, Juraj ; Eden Kym ; Morris, Ryan J. ; MacPhee, Cait E. ; Evans, Martin R. ; Rosalind, Allen J.

Izvornik
Physical Review Letters (0031-9007) 113 (2014); 098101-1

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, pismo, znanstveni

Ključne riječi
Proteins; Self-Assembly; Kinetics; Fluctuations

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Fizika, Biologija

POVEZANOST RADA