Electrostatically tuned rate of peptide self-assembly resolved by multiple particle tracking

Hydrogels formed from the self-assembly of oligopeptides are being extensively studied for biomedical applications. The kinetics of their gelation, as well as a quantitative description of the forces controlling the rate of assembly has not yet been addressed. We report here the use of multiple particle tracking to measure the self-assembly kinetics of the model peptide FKFEFKFE ( KFE8). KFE8 forms well-defined beta-sheet intermediates and is often used as a model peptide system that forms a fibrous network in aqueous solvent. We find that increasing the pH of this system from 3.5 to 4.0 decreases the time of KFE8 gelation by almost hundredfold, from hours to minutes. A remarkable self-similarity between measurements performed at different pH suggests that, although accelerated by the pH increase, gelation follows an invariable mechanism. We propose a semi-quantitative interpretation for the order of magnitudes of gelation time using a simple model for the interaction driving the self-assembly in terms of the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. Such understanding is important for the development of current and future therapeutic applications ( e.g. drug delivery).