Controlled self-assembly of short ß-helical peptides

Cells as functional units from algae to mammals demonstrate the most remarkable degree of self-organization. Processes like membrane formation, protein folding and signal cascades excel in selectivity and control. Nanotechnology is often inspired by biological properties but, despite Nature’s seductive elegance and putative simplicity, often fails at prediction of complex self-assembly. Even weak forces, multiplied by the large number of subunits, contribute to the assemblies and frequently lead to unforeseen results. Membranes are prominent and well understood examples for self-organization and since there is a rising interest in vesicular self-assemblies, the number of potential applications increased with the complexity of the membrane material. The controlled variation of structure and dimension in supramolecular assemblies is a desirable feature for medical and technical applications. From lipids to polymers to the incorporation of proteins: today we are able to tailor membrane properties desirable for many purposes. Highly specific interactions in between membrane constituents are a desirable feature. And when it comes to the discipline of self-assembly, barely a process compares to the specificity and control that is represented by proteins folding into their biologically active state. Thus, it is tempting to exploit this specificity not only in terms of intramolecular but also intermolecular interactions. However, the controlled formation of a membrane from short peptides has not been accomplished to this day. The aim of this work was to construct membranes from peptides, shorter than 30 amino acids in primary structure. The main challenge of the project is the hydrophilic contribution of every amino acid’s backbone that usually constrains the hydrophobic property of peptides. As a consequence, we considered secondary structure as the key to the formation of an entirely peptidic membrane constituent, an assumption that was confirmed by the helical conformation of the antibiotic peptide gramicidin. We present the formation of membranes based on its secondary structure motif and complemented it with varying lengths of positively charged oligo-lysine. The functional property of membrane formation could be assigned to the last seven amino acids of the gramicidin sequence, which allowed us to construct membranes out of peptides only eight amino acids in length. The results are unpreceded both in terms of controlled peptide self-assembly as well as abstraction from the peptides’ biological purpose.