An analytical solution to the kinetics of breakable filament assembly.
We present an analytical treatment of a set of coupled kinetic equations that governs the self-assembly of filamentous molecular structures. Application to the case of protein aggregation demonstrates that the kinetics of amyloid growth can often be dominated by secondary rather than by primary nucleation events. Our results further reveal a range of general features of the growth kinetics of fragmenting filamentous structures, including the existence of generic scaling laws that provide mechanistic information in contexts ranging from in vitro amyloid growth to the in vivo development of mammalian prion diseases.
Knowles
Tuomas P J
TP
Cavendish Laboratory, University of Cambridge, J. J. Thomson Avenue, Cambridge CB3 0HE, UK.
Waudby
Christopher A
CA
Devlin
Glyn L
GL
Cohen
Samuel I A
SI
Aguzzi
Adriano
A
Vendruscolo
Michele
M
Terentjev
Eugene M
EM
Welland
Mark E
ME
Dobson
Christopher M
CM
D000682:Amyloid / Q000737:chemistry*; D001669:Biochemical Phenomena; D005979:Glutathione Peroxidase / Q000737:chemistry; D007328:Insulin / Q000737:chemistry; D007700:Kinetics; D007782:Lactoglobulins / Q000737:chemistry; D055641:Mathematical Concepts; D046912:Multiprotein Complexes / Q000737:chemistry*; D010454:Peptide Termination Factors / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D011328:Prions / Q000737:chemistry; D055503:Protein Multimerization; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry
D000682:Amyloid; D007328:Insulin; D007782:Lactoglobulins; D046912:Multiprotein Complexes; D010454:Peptide Termination Factors; D010455:Peptides; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae