Interactions Between Peptide Assemblies and Proteins for Medicine

Peptide assembly is attractive not only to develop biotechnological tools and smart nanomaterials, but also to treat pathologies in new ways. This Review focuses on recent progress made in the exciting area pertaining the interaction between peptide assemblies and proteins. Earlier works aimed to identify proteins able to bind peptide assemblies for therapeutics' delivery and biocompatible scaffolds. Recent advancements cover more applications that go beyond tissue regeneration and biomaterials. On one hand, self-assembling peptides interacting with proteins can inhibit pathological amyloid fibrillation, or boost the immune response to vaccines. On the other, they have been exploited to promote protein crystallization, also for therapeutics' delivery. As research advances in this exciting area, it opens the way towards a qualitative leap in the clinical translation of supramolecular medicinal chemistry to creatively tackle unmet challenges of modern disease treatment and prevention

Direct observation of adsorption sites of protein impurities and their effects on step advancement of protein crystals

We measured noninvasively step velocities of elementary two-dimensional (2D) islands on {110} faces of tetragonal lysozyme crystals, under various supersaturations, by laser confocal microscopy combined with differential interference contrast microscopy. We studied the correlation between the effects of protein impurities on the growth of elementary steps and their adsorption sites on a crystal surface, using three kinds of proteins: fluorescent-labeled lysozyme (F-lysozyme), covalently bonded dimers of lysozyme (dimer), and a 18 kDa polypeptide (18 kDa). These three protein impurities suppressed the advancement of the steps. However, they exhibited different supersaturation dependencies of the suppression of the step velocities. To clarify the cause of this difference, we observed in situ the adsorption sites of individual molecules of F-lysozyme and fluorescent-labeled dimer (F-dimer) on the crystal surface by single-molecule visualization. We found that F-lysozyme adsorbed preferentially on steps (i.e., kinks), whereas F-dimer adsorbed randomly on terraces. Taking into account the different adsorption sites of F-lysozyme and F-dimer, we could successfully explain the different effects of the impurities on the step velocities. These observations strongly suggest that 18 kDa also adsorbs randomly on terraces. Seikagaku lysozyme exhibited a complex effect that could not alone be explained by the two major impurities (dimer and 18 kDa) present in Seikagaku lysozyme, indicating that trace amounts of other impurities significantly affect the step advancement