A three-stage kinetic model of amyloid fibrillation.

Amyloid fibrillation has been intensively studied because of its association with various neurological disorders. While extensive time-dependent fibrillation experimental data are available and appear similar, few mechanistic models have been developed to unify those results. The aim of this work was to interpret these experimental results via a rigorous mathematical model that incorporates the physical chemistry of nucleation and fibril growth dynamics.

Protein structural perturbation and aggregation on homogeneous surfaces.

We have demonstrated that globular proteins, such as hen egg lysozyme in phosphate buffered saline at room temperature, lose native structural stability and activity when adsorbed onto well-defined homogeneous solid surfaces. This structural loss is evident by alpha-helix to turns/random during the first 30 min and followed by a slow alpha-helix to beta-sheet transition. Increase in intramolecular and intermolecular beta-sheet content suggests conformational rearrangement and aggregation between different protein molecules, respectively.

Effect of surface wettability on the adhesion of proteins.

Besides significantly broadening the scope of available data on adhesion of proteins on solid substrates, we demonstrate for the first time that all seven proteins (tested here) behave similarly with respect to adhesion exhibiting a step increase in adhesion as wettability of the solid substrate decreases. Also, quantitative measures of like-protein-protein and like-self-assembled-monolayer (SAM)-SAM adhesive energies are provided. New correlations, not previously reported, suggest that the helix and random content (as measures of secondary structure) normalized by the molecular weight of a protein are significant for predicting protein adhesion and are likely related to protein stability at interfaces.

Protein unfolding at interfaces: slow dynamics of alpha-helix to beta-sheet transition.

A two-phase sequential dynamic change in the secondary structure of hen egg lysozyme (Lys) adsorbed on solid substrates was observed. The first phase involved fast conversion of alpha-helix to random/turns (within the first minute or at very low coverage or high substrate wettability) with no perceptible change in beta-sheet content. The second phase (1-1200 min), however, involved a relatively slow conversion from alpha-helix to beta-sheet without a noticeable change in random/turns.