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Albany 2015:Book of Abstracts

Albany 2015
Conversation 19
June 9-13 2015
©Adenine Press (2012)

Determination of the Size of Folding Nuclei of Protofibrils from the Concentration Dependence of the Rate and Lag-time of Their Formation

A kinetic model of the process of formation of amyloid protofibrils is suggested, which allows calculation of the size of the nuclei using only kinetic data. This model includes the stage of primary nucleation, the linear growth of protofibrils (proceeding only at the cost of attaching of monomers to their ends) and a possible exponential growth of protofibrils at the cost of either growth from the surface, or fragmentation, or branching with the secondary nuclei. Theoretically, only the exponential growth is compatible with the existence of a pronounced lag-period (which can take much more time than the growth of aggregates themselves). The obtained analytical solution allows us to determine the size of the primary and secondary nuclei from the experimentally obtained concentration dependences of the time of growth and of the ratio of the lag-time duration to the time of growth of amyloid protofibrils (Dovidchenko, Finkelstein, Galzitskaya, 2014). The theoretical results are used to analyze the experimental data taken from literature and our own experimental data on the amyloid formation by insulin and its mutant, LysPro insulin (Selivanova et al., 2014).

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This research has been supported by the Russian Science Foundation Grant 14-14-00536.

References
    N.V. Dovidchenko, A.V. Finkelstein, O.V. Galzitskaya (2014) How to determine the size of folding nuclei of protofibrils from the concentration dependence of the rate and lag-time of aggregation. I. Modeling the amyloid protofibril formation. J Phys. Chem. B, 118(5):1189-1197.

    O.M. Selivanova, M.Y. Suvorina, N.V. Dovidchenko, I.A. Eliseeva, A.K. Surin, A.V. Finkelstein, V.V. Schmatchenko, O.V. Galzitskaya. (2014) How to Determine the Size of Folding Nuclei of Protofibrils from the Concentration Dependence of the Rate and Lag-Time of Aggregation. II. Experimental Application for Insulin and LysPro Insulin: Aggregation Morphology, Kinetics, and Sizes of Nuclei. J Phys Chem B, 118(5): 1198-1206.


Oxana V. Galzitskaya1
Nikita V. Dovidchenko1
Olga M. Selivanova1
Maria Yu. Suvorina1
Alexey K. Surin, 1, 3
Alexey V. Finkelstein 1, 2

1Institute of Protein Research
Russian Academy of Sciences
Pushchino, Moscow Region, 142290, Russia 2Pushchino Branch of the Moscow State Lomonosov University
Pushchino
Moscow Region, 142290, Russia
3State Research Center for Applied Microbiology & Biotechnology
Obolensk, Serpukhov District
Moscow Region, 142279, Russia

Ph: (+74967) 318275
Fx: (+74967) 418435
ogalzit@vega.protres.ru