Understanding the kinetics and thermodynamics of association-dissociation of an amyloid fibril

The mechanistic studies of amyloid accumulation have gained significant momentum in the last few decades due to their implications in functional roles, pathogenicity and potential as biomaterials. However, the underlying molecular-level driving forces for their assembly and disassembly, including stability and spontaneity are not explored, partly due to the failure of establishing a dynamic equilibrium when full-length amyloidogenic proteins are employed. To remove this complexity and to establish the kinetics-thermodynamics parameters for amyloid fibrils, we utilized a small heptapeptide GNNQQNY, which is the core amyloidic part of the Sup35 prion protein of yeast. Using this model peptide, we explored the micro environmental conditions (pH, temperature and molecular crowding) which might be favorable for establishing aggregation-dissociation equilibrium. Further, the stability and spontaneity parameters associated with this are evaluated and the results are supported by the secondary structural changes of the peptide. The study for the first time establishes equilibrium based stability markers for the amyloid fibrils and opens new avenues for their implications in structural and functional heterogeneity in different micro environmental milieu.