Abstract
Understanding the kinetics of peptide self-assembly is important because of the involvement of peptide amyloid fibrils in several neurodegenerative diseases. In this paper, we have studied the dissolution kinetics of self-assembled model peptide fibrils after a dilution quench. Due to the low concentrations involved, the experimental method of choice was isothermal titration calorimetry (ITC). We show that the dissolution is a strikingly slow and reaction-limited process, that can be timescale separated from other rapid processes associated with dilution in the ITC experiment. We argue that the rate-limiting step of dissolution involves the breaking up of inter-peptide –sheet hydrogen bonds, replacing them with peptide–water hydrogen bonds. Complementary pH experiments revealed that the self-assembly involves partial deprotonation of the peptide molecules.
Highlights
Peptide self–assembly has been studied extensively in the last decades
We have studied the dissolution kinetics of self-assembled model peptide fibrils after a dilution quench
We have shown that isothermal titration calorimetry (ITC) experiments can be useful to investigate the thermodynamics, and the dissolution kinetics of peptide aggregates in solution
Summary
Peptide self–assembly has been studied extensively in the last decades. One reason is that peptide aggregation into long fibrillar structures, often referred to as amyloids, is a hallmark of a number of neurodegenerative diseases [1,2,3], including Alzheimer’s and Parkinson’s. In order to understand the consequences of amyloid formation in vivo, we need to address the molecular pathways and kinetics of fibril assembly and disassembly. Recent developments of experimental protocols [11] have allowed for the collection of accurate and reproducible kinetic data of fibril formation. Based on these data, a kinetic model for the fibril formation process could be developed [15], taking into account both primary and secondary nucleation processes. Dissolution kinetics can be of interest for certain applications, e.g., drug administration, and it is interesting to understand assembly and disassembly kinetics from the point of view of microscopic reversibility
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