Nature Commun. 5, 3321 (2014)

Peptides that can disrupt or permeate cell membranes have been exploited in various biomedical applications including gene delivery and as antimicrobials. The interactions between cationic and hydrophobic regions of peptides and cell membranes are well established. Now, Samuel Stupp and colleagues investigate the influence of intermolecular interactions within peptide amphiphiles (PAs) on cell viability and membrane integrity. PAs comprise a peptide chain attached at one end to an alkyl chain and self-assemble into nanofibrous structures. Stupp and colleagues alter the degree of intermolecular hydrogen bonding within the PAs by changing the amino acid sequence whilst keeping the cationic and hydrophobic regions as similar as possible. Coatings formed from PAs with a lower tendency to form β-sheet hydrogen-bonded structures (and, as a result, have reduced intermolecular cohesion) induce cell death in a range of cell lines, however, coatings formed from PAs with increased hydrogen-bonding capability support cell viability. In cell-membrane model studies using liposomes, the PA assemblies with reduced intermolecular cohesion are shown to interact with and disrupt the lipid domains of a phospholipid bilayer.