Protein fibrillation due to elongation and fragmentation of initially appeared fibrils: a simple kinetic model.
The assembly of various proteins into fibrillar aggregates is an important phenomenon with wide implications ranging from human disease to nanoscience. Employing a new model, we analyze the kinetics of protein fibrillation in the case when the process occurs by elongation of initially appeared fibrils which multiply solely by fragmentation, because fibril nucleation is negligible. Owing to its simplicity, our model leads to mathematically friendly and physically clear formulas for the time dependence of the fibrillation degree and for a number of experimental observables such as the maximum fibrillation rate, the fibrillation lag time, and the half-fibrillation time. These formulas provide a mechanistic insight into the kinetics of fragmentation-affected fibrillation of proteins. We confront theory with experiment and find that our model allows a good global description of a large dataset [W.-F. Xue, S. W. Homans, and S. E. Radford, Proc. Natl. Acad. Sci. U.S.A. 105, 8926 (2008)] for the fibrillation kinetics of beta-2 microglobulin. Our analysis leads to new methods for experimental determination of the fibril solubility, elongation rate constant, and nucleation rate from data for the time course of protein fibrillation.
Institute of Physical Chemistry, Bulgarian Academy of Sciences, ul. Acad. G. Bonchev 11, Sofia 1113, Bulgaria.
Dimo
D
Kashchiev
D007700:Kinetics; D008958:Models, Molecular; D011506:Proteins / Q000737:chemistry*
D011506:Proteins