Reversible peptide particle formation using a mini amino acid sequence

Abstract

Interest in nanostructures, artificial compartments and smart materials is steadily increasing as a result of beneficial applications in sensors, tissue engineering, nanoreactors and drug delivery systems. Block copolymers, peptide-based hybrid materials, expressed protein-like copolymers, and peptides that self-assemble in aqueous solution fulfill the demands of such applications while providing maximum biocompatibility. Herein, we focus on the formation of self-assembled particles using an amphiphilic amino acid (AA) sequence derived by solid-phase peptide synthesis (SPPS) and describe its purification and characterisation. The prepared undecamer features a repetitive L-tryptophan and D-leucine [LW-DL] motif representing the hydrophobic block, and an N-terminally attached hydrophilic (lysine or acetylated lysine) section. For peptides containing charged lysine, aggregation into micelles and a minor fraction of peptide particles was observed. Charge shielding with anionic counter ions shifted the equilibrium towards the larger peptide aggregates, with their size depending on the counter ion's position in the Hofmeister series. Similarly, the corresponding uncharged (acetylated) peptide was also demonstrated to assemble into micelles and subsequently into peptide particles, termed ‘peptide beads’, which we hypothesise to be multicompartment micelles. The formation of the peptide beads was studied as a function of temperature and solvent composition by means of electron paramagnetic resonance (EPR), dynamic and static light scattering, fluorimetry and electron microscopy. The results suggest an equilibrium between single peptide molecules, micelles, and peptide beads. Interestingly once formed the peptide beads show high mechanical stability and preserve their shape and dimensions even after isolation from solution.